Plasticity of CD4+ T Cell Lineage Differentiation

Zhou, Liang; Chong, Mark M.W.; Littman, Dan R.

doi:10.1016/j.immuni.2009.05.001

Cited by 1,551T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisIL-33, ST2, and ILC Pathways

Plasticity of CD4+ T Cell Lineage Differentiation

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Zhou, Liang, Chong, Mark M.W., Littman, Dan R.·2009·Immunity

DOI 10.1016/j.immuni.2009.05.001

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Abstract

The differentiation of naive CD4(+) T cells into lineages with distinct effector functions has been considered to be an irreversible event. T helper type 1 (Th1) cells stably express IFN-gamma, whereas Th2 cells express IL-4. The discovery and investigation of two other CD4(+) T cell subsets, induced regulatory T (iTreg) cells and Th17 cells, has led to a rethinking of the notion that helper T cell subsets represent irreversibly differentiated endpoints. Accumulating evidence suggests that CD4(+) T cells, particularly iTreg and Th17 cells, are more plastic than previously appreciated. It appears that expression of Foxp3 by iTreg cells or IL-17 by Th17 cells may not be stable and that there is a great degree of flexibility in their differentiation options. Here, we will discuss recent findings that demonstrate the plasticity of CD4(+) T cell differentiation and the biological implications of this flexibility.

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TH1 cells are responsible for host defense against intracellular microbes and implicated in systemic autoimmunity; TH2 cells fight extracellular parasites and are involved in anaphylactic reactions; TH17 cells mediate immunity against extracellular bacteria and fungi as well as organ-specific autoimmunity.
“The former group encompasses functionally distinct populations including T H 1 cells responsible for host defense against intracellular microbes and implicated in systemic autoimmunity, T H 2 cells that fight off extracellular parasites and are involved in anaphylactic reactions and T H 17 cells that mediate immunity against extracellular bacteria and fungi as well as organspecific autoimmunity (Z”
From Iron in infection and immunity (2020) · cites this paper as Zhou et al., 2009
The current view is that CD4 Th cell subsets are not separate lineages but have plasticity and form a continuum of mixed functional capacities.
“However, the current view is that CD4 Th cell subsets are not separate lineages but have plasticity and form a continuum of mixed functional capacities [177, 178].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [177]

Control of Regulatory T Cell Development by the Transcription Factor Foxp3
Hori, S., Nomura, T., & Sakaguchi, S. (2003) · Science · doi:10.1126/science.1079490 · Cited by 8,187 · see citing works
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003) · Nature Immunology · doi:10.1038/ni904 · Cited by 7,745 · see citing works
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992 · see citing works
The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145 · see citing works
Self-citation
Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
Harrington, L. E., Hatton, R. D., Mangan, P. R., Turner, H., Murphy, T. L., Murphy, K. M., & Weaver, C. T. (2005) · Nature Immunology · doi:10.1038/ni1254 · Cited by 4,742 · see citing works
Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
Chen, W., Jin, W., Hardegen, N. J., Lei, K.-J., Li, L., Marinos, N. J., McGrady, G., & Wahl, S. M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030152 · Cited by 4,678 · see citing works
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y.-H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., et al. (2005) · Nature Immunology · doi:10.1038/ni1261 · Cited by 4,265 · see citing works
TGFβ in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.001 · Cited by 3,605 · see citing works
How regulatory T cells work
Vignali, D. A. A., Collison, L. W., & Workman, C. J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2343 · Cited by 3,463 · see citing works
Transforming growth factor-β induces development of the TH17 lineage
Mangan, P. R., Harrington, L. E., O'Quinn, D. B., Helms, W. S., Bullard, D. C., Elson, C. O., Hatton, R. D., Wahl, S. M., Schoeb, T. R., & Weaver, C. T. (2006) · Nature · doi:10.1038/nature04754 · Cited by 3,087 · see citing works
An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System
Mazmanian, S. K., Liu, C. H., Tzianabos, A. O., & Kasper, D. L. (2005) · Cell · doi:10.1016/j.cell.2005.05.007 · Cited by 2,910 · see citing works
An essential role for Scurfin in CD4+CD25+ T regulatory cells
Khattri, R., Cox, T., Yasayko, S.-A., & Ramsdell, F. (2003) · Nature Immunology · doi:10.1038/ni909 · Cited by 2,860 · see citing works
A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β– and retinoic acid–dependent mechanism
Coombes, J. L., Siddiqui, K. R. R., Arancibia-Cárcamo, C. V., Hall, J. A., Sun, C., Belkaid, Y., & Powrie, F. M. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070590 · Cited by 2,708 · see citing works
A microbial symbiosis factor prevents intestinal inflammatory disease
Mazmanian, S. K., Round, J. L., & Kasper, D. L. (2008) · Nature · doi:10.1038/nature07008 · Cited by 2,340 · see citing works
Toll Pathway-Dependent Blockade of CD4+CD25+ T Cell-Mediated Suppression by Dendritic Cells
Pasare, C., & Medzhitov, R. (2003) · Science · doi:10.1126/science.1078231 · Cited by 2,327 · see citing works
Regulatory T Cell Lineage Specification by the Forkhead Transcription Factor Foxp3
Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J., Farr, A. G., & Rudensky, A. Y. (2005) · Immunity · doi:10.1016/j.immuni.2005.01.016 · Cited by 2,255 · see citing works
IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways
Zhou, L., Ivanov, I. I., Spolski, R. J., Min, R., Shenderov, K., Egawa, T., Levy, D. E., Leonard, W. J., & Littman, D. R. (2007) · Nature Immunology · doi:10.1038/ni1488 · Cited by 2,134 · see citing works
Self-citation
Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis
Zheng, Y., Danilenko, D., Valdez, P., Kasman, I., Eastham-Anderson, J., Wu, J., & Ouyang, W. (2007) · Nature · doi:10.1038/nature05505 · Cited by 2,034 · see citing works
Reciprocal T H 17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid
Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., & Cheroutre, H. (2007) · Science · doi:10.1126/science.1145697 · Cited by 1,982 · see citing works
Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid
Sun, C., Hall, J. A., Blank, R. B., Bouladoux, N. J., Oukka, M., Mora, J. R., & Belkaid, Y. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070602 · Cited by 1,880 · see citing works
TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function
Zhou, L., Lopes, J. E., Chong, M. M. W., Ivanov, I. I., Min, R., Victora, G. D., Shen, Y., Du, J., Rubtsov, Y. P., Rudensky, A. Y., et al. (2008) · Nature · doi:10.1038/nature06878 · Cited by 1,866 · see citing works
Self-citation
IL-17 family cytokines and the expanding diversity of effector T cell lineages
Weaver, C. T., Hatton, R. D., Mangan, P. R., & Harrington, L. E. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141557 · Cited by 1,842 · see citing works
Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice
Kim, J. M., Rasmussen, J. P., & Rudensky, A. Y. (2006) · Nature Immunology · doi:10.1038/ni1428 · Cited by 1,827 · see citing works
Specific Microbiota Direct the Differentiation of IL-17-Producing T-Helper Cells in the Mucosa of the Small Intestine
Ivanov, I. I., Frutos, R. D. L., Manel, N., Yoshinaga, K., Rifkin, D. B., Sartor, R. B., Finlay, B. B., & Littman, D. R. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.09.009 · Cited by 1,770 · see citing works
Self-citation
Mechanisms of Foxp3+ T Regulatory Cell-Mediated Suppression
Shevach, E. M. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.010 · Cited by 1,754 · see citing works
T Helper 17 Lineage Differentiation Is Programmed by Orphan Nuclear Receptors RORα and RORγ
Yang, X. O., Pappu, B. P., Nurieva, R., Akimzhanov, A., Kang, H. S., Chung, Y., Ma, L., Shah, B., Panopoulos, A. D., Schluns, K. S., et al. (2008) · Immunity · doi:10.1016/j.immuni.2007.11.016 · Cited by 1,605 · see citing works
TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell–mediated pathology
McGeachy, M. J., Bak-Jensen, K. S., Chen, Y., Tato, C. M., Blumenschein, W., McClanahan, T., & Cua, D. J. (2007) · Nature Immunology · doi:10.1038/ni1539 · Cited by 1,520 · see citing works
Interleukin-2 Signaling via STAT5 Constrains T Helper 17 Cell Generation
Laurence, A., Tato, C. M., Davidson, T. S., Kanno, Y., Chen, Z., Yao, Z., Blank, R. B., Meylan, F., Siegel, R., Hennighausen, L., et al. (2007) · Immunity · doi:10.1016/j.immuni.2007.02.009 · Cited by 1,507 · see citing works
STAT3 Regulates Cytokine-mediated Generation of Inflammatory Helper T Cells
Yang, X. O., Panopoulos, A. D., Nurieva, R., Chang, S. H., Wang, D., Watowich, S. S., & Dong, C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c600321200 · Cited by 1,494 · see citing works
Epigenetic Control of the foxp3 Locus in Regulatory T Cells
Floess, S., Freyer, J., Siewert, C., Baron, U., Olek, S., Polansky, J. K., Schlawe, K., Chang, H., Bopp, T., Schmitt, E., et al. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050038 · Cited by 1,272 · see citing works
Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages
Nurieva, R. I., Chung, Y., Hwang, D., Yang, X. O., Kang, H. S., Ma, L., Wang, Y.-H., Watowich, S. S., Jetten, A. M., Tian, Q., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.009 · Cited by 1,205 · see citing works
Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17
LeibundGut-Landmann, S., Groß, O., Robinson, M. J., Osorio, F., Slack, E. C., Tsoni, S. V., Schweighoffer, E., Tybulewicz, V., Brown, G. D., Ruland, J., et al. (2007) · Nature Immunology · doi:10.1038/ni1460 · Cited by 1,191 · see citing works
Global Mapping of H3K4me3 and H3K27me3 Reveals Specificity and Plasticity in Lineage Fate Determination of Differentiating CD4+ T Cells
Wei, G., Wei, L., Zhu, J., Zang, C., Hu-Li, J., Yao, Z., Cui, K., Kanno, Y., Roh, T.-Y., Watford, W. T., et al. (2009) · Immunity · doi:10.1016/j.immuni.2008.12.009 · Cited by 1,152 · see citing works
Molecular Antagonism and Plasticity of Regulatory and Inflammatory T Cell Programs
Yang, X. O., Nurieva, R., Martínez, G., Kang, H. S., Chung, Y., Pappu, B. P., Shah, B., Chang, S. H., Schluns, K. S., Watowich, S. S., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.007 · Cited by 1,129 · see citing works
Foxp3-dependent programme of regulatory T-cell differentiation
Gavin, M. A., Rasmussen, J. P., Fontenot, J. D., Vasta, V., Manganiello, V. C., Beavo, J. A., & Rudensky, A. Y. (2007) · Nature · doi:10.1038/nature05543 · Cited by 1,127 · see citing works
ATP drives lamina propria TH17 cell differentiation
Atarashi, K., Nishimura, J., Shima, T., Umesaki, Y., Yamamoto, M., Onoue, M., Yagita, H., Ishii, N., Evans, R., Honda, K., et al. (2008) · Nature · doi:10.1038/nature07240 · Cited by 1,089 · see citing works
Natural and Adaptive Foxp3+ Regulatory T Cells: More of the Same or a Division of Labor?
de Lafaille, M. A. C., & Lafaille, J. J. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.002 · Cited by 1,057 · see citing works
Late Developmental Plasticity in the T Helper 17 Lineage
Lee, Y. K., Turner, H., Maynard, C. L., Oliver, J. R., Chen, D., Elson, C. O., & Weaver, C. T. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.005 · Cited by 1,053 · see citing works
T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells
Afkarian, M., Šedý, J. R., Yang, J., Jacobson, N. G., Cereb, N., Yang, S. Y., Murphy, T. L., & MURPHY, K. M. M. (2002) · Nature Immunology · doi:10.1038/ni794 · Cited by 1,038 · see citing works
TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells
Marie, J. C., Letterio, J. J., Gavin, M. A., & Rudensky, A. Y. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042276 · Cited by 986 · see citing works
Regulation of the Interleukin (IL)-12R β2 Subunit Expression in Developing T Helper 1 (Th1) and Th2 Cells
Szabo, S. J., Dighe, A. S., Gubler, U., & MURPHY, K. M. M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.5.817 · Cited by 973 · see citing works
Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses
Zheng, Y., Chaudhry, A., Kas, A., deRoos, P., Kim, J. M., Chu, T.-T., Corcoran, L., Treuting, P., Klein, U., & Rudensky, A. Y. (2009) · Nature · doi:10.1038/nature07674 · Cited by 958 · see citing works
Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system
Stumhofer, J. S., Laurence, A., Wilson, E. H., Huang, E., Tato, C. M., Johnson, L. M., Villarino, A. V., Huang, Q., Yoshimura, A., Sehy, D., et al. (2006) · Nature Immunology · doi:10.1038/ni1376 · Cited by 955 · see citing works
All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation
Benson, M. J., Pino-Lagos, K., Rosemblatt, M., & Noelle, R. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070719 · Cited by 847 · see citing works
Helper T Cell Differentiation Is Controlled by the Cell Cycle
Bird, J. J., Brown, D. R., Mullen, A. C., Moskowitz, N. H., Mahowald, M. A., Sider, J. R., Gajewski, T. F., Wang, C.-R., & Reiner, S. L. (1998) · Immunity · doi:10.1016/s1074-7613(00)80605-6 · Cited by 834 · see citing works
Role of T-bet in Commitment of T H 1 Cells Before IL-12-Dependent Selection
Mullen, A. C., High, F. A., Hutchins, A. S., Lee, H. W., Villarino, A. V., Livingston, D. M., Kung, A. L., Cereb, N., Yao, T., Yang, S. Y., et al. (2001) · Science · doi:10.1126/science.1059835 · Cited by 825 · see citing works
Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17–producing T cells
Batten, M., Li, J., Yi, S., Kljavin, N. M., Danilenko, D. M., Lucas, S., Lee, J., de Sauvage, F. J., & Ghilardi, N. (2006) · Nature Immunology · doi:10.1038/ni1375 · Cited by 815 · see citing works
Transforming Growth Factor-β Controls Development, Homeostasis, and Tolerance of T Cells by Regulatory T Cell-Dependent and -Independent Mechanisms
Li, M. O., Sanjabi, S., & Flavell, R. A. (2006) · Immunity · doi:10.1016/j.immuni.2006.07.011 · Cited by 794 · see citing works
DNA methylation controls Foxp3 gene expression
Polansky, J. K., Kretschmer, K., Freyer, J., Floess, S., Garbe, A. I., Baron, U., Olek, S., Hamann, A., von Boehmer, H., & Huehn, J. (2008) · European Journal of Immunology · doi:10.1002/eji.200838105 · Cited by 787 · see citing works
Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein
Lu, L., Thai, T., Calado, D. P., Chaudhry, A., Kubo, M., Tanaka, K., Loeb, G. B., Lee, H., Yoshimura, A., Rajewsky, K., et al. (2009) · Immunity · doi:10.1016/j.immuni.2008.11.010 · Cited by 784 · see citing works
A Fundamental Role for Interleukin-21 in the Generation of T Follicular Helper Cells
Vogelzang, A., McGuire, H. M., Yu, D., Sprent, J., Mackay, C. R., & King, C. (2008) · Immunity · doi:10.1016/j.immuni.2008.06.001 · Cited by 738 · see citing works
Human CD25highFoxp3pos regulatory T cells differentiate into IL-17–producing cells
Koenen, H. J. P. M., Smeets, R. L., Vink, P. M., van Rijssen, E., Boots, A. M. H., & Joosten, I. (2008) · Blood · doi:10.1182/blood-2008-01-133967 · Cited by 735 · see citing works
Cutting Edge: Regulatory T Cells Induce CD4+CD25−Foxp3− T Cells or Are Self-Induced to Become Th17 Cells in the Absence of Exogenous TGF-β
Xu, L., Kitani, A., Fuss, I. J., & Strober, W. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.6725 · Cited by 733 · see citing works
DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells
Baron, U., Floess, S., Wieczorek, G., Baumann, K., Grützkau, A., Dong, J., Thiel, A., Boeld, T. J., Hoffmann, P., Edinger, M., et al. (2007) · European Journal of Immunology · doi:10.1002/eji.200737594 · Cited by 694 · see citing works
Identification of IL-17-producing FOXP3 + regulatory T cells in humans
Voo, K. S., Wang, Y., Santori, F. R., Boggiano, C., Wang, Y.-H., Arima, K., Bover, L. C., Hanabuchi, S., Khalili, J. S., Marinova, E., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900408106 · Cited by 693 · see citing works
Self-citation
Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1
Ono, M., Yaguchi, H., Ohkura, N., Kitabayashi, I., Nagamura, Y., Nomura, T., Miyachi, Y., Tsukada, T., & Sakaguchi, S. (2007) · Nature · doi:10.1038/nature05673 · Cited by 692 · see citing works
The development of inflammatory TH-17 cells requires interferon-regulatory factor 4
Brüstle, A., Heink, S., Huber, M., Rosenplänter, C., Stadelmann, C., Yu, P., Arpaia, E., Mak, T. W., Kamradt, T., & Lohoff, M. D. (2007) · Nature Immunology · doi:10.1038/ni1500 · Cited by 691 · see citing works
Epigenetic control of T-helper-cell differentiation
Wilson, C. B., Rowell, E. A., & Sekimata, M. (2009) · Nature reviews. Immunology · doi:10.1038/nri2487 · Cited by 678 · see citing works
Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells
Chen, Z. J., Laurence, A. D. J., Kanno, Y., Pacher-Zavisin, M. C., Zhu, B., Tato, C. M., Yoshimura, A., Hennighausen, L. G., & O’Shea, J. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600666103 · Cited by 652 · see citing works
CREB/ATF-dependent T cell receptor–induced FoxP3 gene expression: a role for DNA methylation
Kim, H., & Leonard, W. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070109 · Cited by 597 · see citing works
Follicular Helper T Cells: Lineage and Location
Fazilleau, N., Mark, L., McHeyzer‐Williams, L. J., & McHeyzer‐Williams, M. G. (2009) · Immunity · doi:10.1016/j.immuni.2009.03.003 · Cited by 593 · see citing works
Preferential Generation of Follicular B Helper T Cells from Foxp3 + T Cells in Gut Peyer's Patches
Tsuji, M., Komatsu, N., Kawamoto, S., Suzuki, K., Kanagawa, O., Honjo, T., Hori, S., & Fagarasan, S. (2009) · Science · doi:10.1126/science.1169152 · Cited by 592 · see citing works
Control of Regulatory T Cell Lineage Commitment and Maintenance
Josefowicz, S. Z., & Rudensky, A. Y. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.009 · Cited by 572 · see citing works
Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice
Bending, D., Peña, H. D. L., Veldhoen, M., Phillips, J. M., Uyttenhove, C., Stockinger, B., & Cooke, A. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37865 · Cited by 559 · see citing works
Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells
Djuretic, I. M., Levanon, D., Negreanu, V., Groner, Y., Rao, A., & Ansel, K. M. (2006) · Nature Immunology · doi:10.1038/ni1424 · Cited by 532 · see citing works
Cutting Edge: Role of IL-27/WSX-1 Signaling for Induction of T-Bet Through Activation of STAT1 During Initial Th1 Commitment
Takeda, A., Hamano, S., Yamanaka, A., Hanada, T., Ishibashi, T., Mak, T. W., Yoshimura, A., & Yoshida, H. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.10.4886 · Cited by 530 · see citing works
Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity
Zhou, X., Jeker, L. T., Fife, B. T., Zhu, S., Anderson, M. S., McManus, M. T., & Bluestone, J. A. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080707 · Cited by 528 · see citing works
Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage?
Huehn, J., Polansky, J. K., & Hamann, A. (2008) · Nature reviews. Immunology · doi:10.1038/nri2474 · Cited by 527 · see citing works
Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells
Veldhoen, M., Hirota, K., Christensen, J. R., O’Garra, A., & Stockinger, B. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20081438 · Cited by 522 · see citing works
Coordination of Early Protective Immunity to Viral Infection by Regulatory T Cells
Lund, J. M., Hsing, L., Pham, T., & Rudensky, A. Y. (2008) · Science · doi:10.1126/science.1155209 · Cited by 514 · see citing works
Interactions among the transcription factors Runx1, RORγt and Foxp3 regulate the differentiation of interleukin 17–producing T cells
Zhang, F., Meng, G., & Strober, W. (2008) · Nature Immunology · doi:10.1038/ni.1663 · Cited by 501 · see citing works
Commensal DNA Limits Regulatory T Cell Conversion and Is a Natural Adjuvant of Intestinal Immune Responses
Hall, J. A., Bouladoux, N. J., Sun, C., Wohlfert, E. A., Blank, R. B., Zhu, Q., Grigg, M. E., Berzofsky, J. A., & Belkaid, Y. (2008) · Immunity · doi:10.1016/j.immuni.2008.08.009 · Cited by 490 · see citing works
Early Transcription and Silencing of Cytokine Genes Underlie Polarization of T Helper Cell Subsets
Grogan, J. L., Mohrs, M., Harmon, B., Lacy, D. A., Sedat, J. W., & Locksley, R. M. (2001) · Immunity · doi:10.1016/s1074-7613(01)00103-0 · Cited by 485 · see citing works
IL-17–producing human peripheral regulatory T cells retain suppressive function
Bériou, G., Costantino, C. M., Ashley, C. W., Yang, L., Kuchroo, V. K., Baecher‐Allan, C., & Hafler, D. A. (2009) · Blood · doi:10.1182/blood-2008-10-183251 · Cited by 482 · see citing works
IL-27 regulates IL-12 responsiveness of naïve CD4 + T cells through Stat1-dependent and -independent mechanisms
Lucas, S., Ghilardi, N., Li, J., & de Sauvage, F. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2536517100 · Cited by 460 · see citing works
Signals mediated by transforming growth factor-β initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease
Veldhoen, M., Hocking, R. J., Flavell, R., & Stockinger, B. (2006) · Nature Immunology · doi:10.1038/ni1391 · Cited by 459 · see citing works
Reversibility of T helper 1 and 2 populations is lost after long-term stimulation.
Murphy, E., Shibuya, K., Hosken, N. A., Openshaw, P., Maino, V. C., Davis, K. A., MURPHY, K. M. M., & O’Garra, A. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.3.901 · Cited by 435 · see citing works
An epigenetic view of helper T cell differentiation
Ansel, K. M., Lee, D. U., & Rao, A. (2003) · Nature Immunology · doi:10.1038/ni0703-616 · Cited by 419 · see citing works
Anomalous Type 17 Response to Viral Infection by CD8 + T Cells Lacking T-bet and Eomesodermin
Intlekofer, A. M., Banerjee, A., Takemoto, N., Gordon, S. M., DeJong, C. S., Shin, H., Hunter, C. A., Wherry, E. J., Lindsten, T., & Reiner, S. L. (2008) · Science · doi:10.1126/science.1159806 · Cited by 394 · see citing works
IL-4–producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells
King, I. L., & Mohrs, M. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090313 · Cited by 393 · see citing works
T follicular helper cells differentiate from Th2 cells in response to helminth antigens
Zaretsky, A. G., Taylor, J. J., King, I. L., Marshall, F. A., Mohrs, M., & Pearce, E. J. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090303 · Cited by 384 · see citing works
The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease
Chong, M. M. W., Rasmussen, J. P., Rudensky, A. Y., & Littman, D. R. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20081219 · Cited by 362 · see citing works
Self-citation
Cutting Edge: Foxp3+CD4+CD25+ Regulatory T Cells Induced by IL-2 and TGF-β Are Resistant to Th17 Conversion by IL-6
Zheng, S. G., Wang, J., & Horwitz, D. A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.11.7112 · Cited by 357 · see citing works
Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation
Chen, Z., Laurence, A., & O'Shea, J. J. (2007) · Seminars in Immunology · doi:10.1016/j.smim.2007.10.015 · Cited by 274 · see citing works
DC activated via dectin‐1 convert Treg into IL‐17 producers
Osorio, F., LeibundGut‐Landmann, S., Lochner, M., Lahl, K., Sparwasser, T. D., Eberl, G., & Sousa, C. R. E. (2008) · European Journal of Immunology · doi:10.1002/eji.200838950 · Cited by 273 · see citing works
Repression of interleukin-4 in T helper type 1 cells by Runx/Cbfβ binding to the Il4 silencer
Naoe, Y., Setoguchi, R., Akiyama, K., Muroi, S., Kuroda, M., Hatam, F., Littman, D. R., & Taniuchi, I. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062456 · Cited by 242 · see citing works
Self-citation
Isoform-Specific Inhibition of RORα-Mediated Transcriptional Activation by Human FOXP3
Du, J., Huang, C., Zhou, B., & Ziegler, S. F. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.7.4785 · Cited by 234 · see citing works
Growth Factor Independent-1 Induced by IL-4 Regulates Th2 Cell Proliferation
Zhu, J., Guo, L., Min, B., Watson, C. J., Hu‐Li, J., Young, H. A., Tsichlis, P. N., & Paul, W. E. (2002) · Immunity · doi:10.1016/s1074-7613(02)00317-5 · Cited by 217 · see citing works
Th memory for interleukin‐17 expression is stable in vivo
Lexberg, M. H., Taubner, A., Förster, A., Albrecht, I., Richter, A., Kamradt, T., Radbruch, A., & Chang, H. (2008) · European Journal of Immunology · doi:10.1002/eji.200838541 · Cited by 152 · see citing works
ATP drives lamina propria TH17 cell differentiation
新, 幸. (2009) · Cited by 147 · see citing works
Down-regulation of Gfi-1 expression by TGF-β is important for differentiation of Th17 and CD103+ inducible regulatory T cells
Zhu, J., Davidson, T. S., Wei, G., Jankovic, D. L., Cui, K., Schones, D. E., Guo, L., Zhao, K., Shevach, E. M., & Paul, W. E. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20081666 · Cited by 145 · see citing works
T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype
Mathur, A. N. (2006) · Blood · doi:10.1182/blood-2006-04-015016 · Cited by 143 · see citing works
T-bet and Eomesodermin Play Critical Roles in Directing T Cell Differentiation to Th1 versus Th17
Yang, Y., Xu, J., Niu, Y., Bromberg, J. S., & Ding, Y. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.12.8700 · Cited by 130 · see citing works
Disease in the scurfy (sf) mouse is associated with overexpression of cytokine genes
Kanangat, S., Blair, P. J., Reddy, R., Deheshia, M., Godfrey, V., Rouse, B. T., & Wilkinson, E. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260125 · Cited by 117 · see citing works
Epigenetic inheritance of DNA methylation limits activation-induced expression of FOXP3 in conventional human CD25-CD4+ T cells
Nagar, M., Vernitsky, H., Cohen, Y., Dominissini, D., Berkun, Y., Rechavi, G., Amariglio, N., & Goldstein, I. (2008) · International Immunology · doi:10.1093/intimm/dxn062 · Cited by 77 · see citing works
Functional Plasticity in Memory T Helper Cell Responses
Krawczyk, C. M., Shen, H., & Pearce, E. J. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.7.4080 · Cited by 76 · see citing works
Is selection for TCR affinity a factor in cytokine polarization?
Boyton, R. J., & Altmann, D. M. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02319-0 · Cited by 75 · see citing works
New advances in Clostridium difficile infection: changing epidemiology, diagnosis, treatment and control
DuPont, H. L., Garey, K. W., Caeiro, J., & Jiang, Z. (2008) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0b013e32830f9397 · Cited by 66 · see citing works
Cutting Edge: An IL-17F-CreEYFP Reporter Mouse Allows Fate Mapping of Th17 Cells
Croxford, A. L., Kurschus, F. C., & Waisman, A. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.182.3.1237 · Cited by 48 · see citing works
Long-range regulation of cytokine gene expression
Rowell, E. A., Merkenschlager, M., & Wilson, C. B. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2008.03.012 · Cited by 27 · see citing works
RNAi and chromatin in T cell development and function
Merkenschlager, M., & Wilson, C. B. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2008.03.013 · Cited by 17 · see citing works

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Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis
Meijer, L., Nelson, D. J., Riazanski, V., Gabdoulkhakova, A. G., Héry-Arnaud, G., Berre, R. L., Loaëc, N., Oumata, N., Galons, H., Nowak, E., et al. (2016) · Journal of Innate Immunity · doi:10.1159/000444256 · Cited by 4,992 · see citing works
Follicular Helper CD4 T Cells (T FH )
Crotty, S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101400 · Cited by 2,738 · see citing works
Genetic and epigenetic fine mapping of causal autoimmune disease variants
Farh, K. K.-H., Marson, A., Zhu, J., Kleinewietfeld, M., Housley, W. J., Beik, S., Shoresh, N., Whitton, H., Ryan, R. J. H., Shishkin, A. A., et al. (2015) · Nature · doi:10.1038/nature13835 · Cited by 1,956 · see citing works
Chemokines and Chemokine Receptors: Positioning Cells for Host Defense and Immunity
Griffith, J. W., Sokol, C. L., & Luster, A. D. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120145 · Cited by 2,044 · see citing works
Inflammatory bowel disease
Kaser, A., Zeissig, S., & Blumberg, R. S. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101225 · Cited by 1,806 · see citing works
The Key Role of Segmented Filamentous Bacteria in the Coordinated Maturation of Gut Helper T Cell Responses
Gaboriau-Routhiau, V., Rakotobe, S., Lécuyer, E., Mulder, I., Lan, A., Bridonneau, C., Rochet, V., Pisi, A., De Paepe, M., Brandi, G., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.020 · Cited by 1,452 · see citing works
Generation of pathogenic TH17 cells in the absence of TGF-β signalling
Ghoreschi, K., Laurence, A., Yang, X.-P., Tato, C. M., McGeachy, M. J., Konkel, J. E., Ramos, H. L., Wei, L., Davidson, T. S., Bouladoux, N., et al. (2010) · Nature · doi:10.1038/nature09447 · Cited by 1,388 · see citing works
Mechanisms Underlying Lineage Commitment and Plasticity of Helper CD4 + T Cells
O’Shea, J. J., & Paul, W. E. (2010) · Science · doi:10.1126/science.1178334 · Cited by 1,338 · see citing works
Foxp3+ follicular regulatory T cells control the germinal center response
Linterman, M. A., Pierson, W., Lee, S. K., Kallies, A., Kawamoto, S., Rayner, T. F., Srivastava, M., Divekar, D. P., Beaton, L., Hogan, J. J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2425 · Cited by 1,292 · see citing works
Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery
Nicolas, J., Mura, S., Brambilla, D., Mackiewicz, N., & Couvreur, P. (2013) · Chem. Soc. Rev. · doi:10.1039/c2cs35265f · Cited by 1,270 · see citing works
The Transcriptional Repressor Bcl-6 Directs T Follicular Helper Cell Lineage Commitment
Yu, D., Rao, S., Tsai, L. M., Lee, S. K., He, Y., Sutcliffe, E. L., Srivastava, M., Linterman, M. A., Zheng, L., Simpson, N., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.07.002 · Cited by 1,216 · see citing works
Fate mapping of IL-17-producing T cells in inflammatory responses
Hirota, K., Duarte, J. H., Veldhoen, M., Hornsby, E., Li, Y., Cua, D. J., Ahlfors, H., Wilhelm, C., Tolaini, M., Menzel, U., et al. (2011) · Nature Immunology · doi:10.1038/ni.1993 · Cited by 1,176 · see citing works
Natural and Adaptive Foxp3+ Regulatory T Cells: More of the Same or a Division of Labor?
de Lafaille, M. A. C., & Lafaille, J. J. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.002 · Cited by 1,057 · see citing works
Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity
Mantovani, A., Dinarello, C. A., Molgora, M., & Garlanda, C. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.012 · Cited by 1,046 · see citing works
Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression
Schmiedel, B. J., Singh, D., Madrigal, A., Valdovino-Gonzalez, A. G., White, B. M., Zapardiel-Gonzalo, J., Ha, B., Altay, G., Greenbaum, J. A., McVicker, G., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.022 · Cited by 867 · see citing works
Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
Cossarizza, A., Chang, H., Radbruch, A., Acs, A., Adam, D., Adam‐Klages, S., Agace, W. W., Aghaeepour, N., Akdiş, M., Allez, M., et al. (2019) · European Journal of Immunology · doi:10.1002/eji.201970107 · Cited by 982 · see citing works
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Hu, X., & Ivashkiv, L. B. (2009) · Immunity · doi:10.1016/j.immuni.2009.09.002 · Cited by 928 · see citing works
The Balance of Th17 versus Treg Cells in Autoimmunity
Lee, G. R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030730 · Cited by 868 · see citing works
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Malek, T. R., & Castro, I. (2010) · Immunity · doi:10.1016/j.immuni.2010.08.004 · Cited by 852 · see citing works
Microbial Dysbiosis in Colorectal Cancer (CRC) Patients
Sobhani, I., Tap, J., Roudot‐Thoraval, F., Roperch, J. P., Letulle, S., Langella, P., Corthier, G., Nhieu, J. T. V., & Furet, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016393 · Cited by 832 · see citing works
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Allen, J. E., & Maizels, R. M. (2011) · Nature reviews. Immunology · doi:10.1038/nri2992 · Cited by 831 · see citing works
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Tay, R. E., Richardson, E. K., & Toh, H. C. (2020) · Cancer Gene Therapy · doi:10.1038/s41417-020-0183-x · Cited by 801 · see citing works
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Kolev, M. V., & Kemper, C. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00001 · Cited by 818 · see citing works
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Feske, S., Wulff, H., & Skolnik, E. Y. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112212 · Cited by 764 · see citing works
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Seif, F., Khoshmirsafa, M., Aazami, H., Mohsenzadegan, M., Sedighi, G. R., & Bahar, M. (2017) · Cell Communication and Signaling · doi:10.1186/s12964-017-0177-y · Cited by 774 · see citing works
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Harding, F., Stickler, M. M., Razo, J., & DuBridge, R. B. (2010) · mAbs · doi:10.4161/mabs.2.3.11641 · Cited by 743 · see citing works
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Cerf-Bensussan, N., & Gaboriau-Routhiau, V. (2010) · Nature Reviews Immunology · doi:10.1038/nri2850 · Cited by 704 · see citing works
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Wynn, T. A. (2015) · Nature reviews. Immunology · doi:10.1038/nri3831 · Cited by 671 · see citing works
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Lee, J., Taneja, V., & Vassallo, R. (2011) · Journal of Dental Research · doi:10.1177/0022034511421200 · Cited by 672 · see citing works
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Rao, R. R., Li, Q., Odunsi, K., & Shrikant, P. A. (2010) · Immunity · doi:10.1016/j.immuni.2009.10.010 · Cited by 656 · see citing works
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Hogg, S. J., Beavis, P. A., Dawson, M. A., & Johnstone, R. W. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0077-5 · Cited by 653 · see citing works
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Qiu, F., Liang, C.-L., Liu, H., Zeng, Y., Hou, S., Huang, S. M., Lai, X., & Dai, Z. (2016) · Oncotarget · doi:10.18632/oncotarget.13613 · Cited by 628 · see citing works
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Strzelak, A., Ratajczak, A., Adamiec, A., & Feleszko, W. (2018) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph15051033 · Cited by 631 · see citing works
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Wallace, K. L. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i1.6 · Cited by 581 · see citing works
The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation
Chang, H.-C., Sehra, S., Goswami, R., Yao, W., Yu, Q., Stritesky, G. L., Jabeen, R., McKinley, C., Ahyi, A.-N., Han, L., et al. (2010) · Nature Immunology · doi:10.1038/ni.1867 · Cited by 577 · see citing works
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Josefowicz, S. Z., & Rudensky, A. Y. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.009 · Cited by 572 · see citing works
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Bilate, A. M., & Lafaille, J. J. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075043 · Cited by 569 · see citing works
Guidelines for the use of flow cytometry and cell sorting in immunological studies *
Cossarizza, A., Chang, H., Radbruch, A., Akdiş, M., Andrä, I., Annunziato, F., Bächer, P., Barnaba, V., Battistini, L., Bauer, W. M., et al. (2017) · European Journal of Immunology · doi:10.1002/eji.201646632 · Cited by 572 · see citing works
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Ruterbusch, M., Pruner, K. B., Shehata, L., & Pepper, M. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-103019-085803 · Cited by 550 · see citing works
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Mitsdoerffer, M., Lee, Y., Jäger, A., Kim, H.-J., Korn, T., Kolls, J. K., Cantor, H., Bettelli, E., & Kuchroo, V. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009234107 · Cited by 534 · see citing works
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Han, A. S., Glanville, J., Hansmann, L., & Davis, M. M. (2014) · Nature Biotechnology · doi:10.1038/nbt.2938 · Cited by 534 · see citing works
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531 · see citing works
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English, K. (2012) · Immunology and Cell Biology · doi:10.1038/icb.2012.56 · Cited by 524 · see citing works
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DeNardo, D. G., Andreu, P., & Coussens, L. M. (2010) · Cancer and Metastasis Reviews · doi:10.1007/s10555-010-9223-6 · Cited by 513 · see citing works
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DuPage, M. J. P., & Bluestone, J. A. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2015.18 · Cited by 507 · see citing works
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Fagarasan, S., Kawamoto, S., Kanagawa, O., & Suzuki, K. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101314 · Cited by 501 · see citing works
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Li, L., Huang, L., Vergis, A. L., Ye, H., Bajwa, A., Narayan, V., Strieter, R. M., Rosin, D. L., & Okusa, M. D. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38702 · Cited by 485 · see citing works
Effector T cell plasticity: flexibility in the face of changing circumstances
Murphy, K. M., & Stockinger, B. (2010) · Nature Immunology · doi:10.1038/ni.1899 · Cited by 482 · see citing works
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Speiser, D. E., Chijioke, O., Schaeuble, K., & Münz, C. (2023) · Nature Cancer · doi:10.1038/s43018-023-00521-2 · Cited by 486 · see citing works
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Gao, Y., Nish, S. A., Jiang, R., Hou, L., Licona-Limón, P., Weinstein, J. S., Zhao, H., & Medzhitov, R. M. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.028 · Cited by 478 · see citing works
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Wang, R., & Green, D. R. (2012) · Nature Immunology · doi:10.1038/ni.2386 · Cited by 457 · see citing works
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Perera, G. K., Meglio, P. D., & Nestle, F. O. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011811-132448 · Cited by 464 · see citing works
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Matta, S. M., Hill‐Yardin, E. L., & Crack, P. J. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.04.037 · Cited by 414 · see citing works
RNA modifications: importance in immune cell biology and related diseases
Cui, L., Ma, R., Cai, J., Guo, C., Chen, Z., Yao, L., Wang, Y., Fan, R., Wang, X., & Shi, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01175-9 · Cited by 423 · see citing works
Human T Regulatory Cell Therapy: Take a Billion or So and Call Me in the Morning
Riley, J. L., June, C. H., & Blazar, B. R. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.006 · Cited by 412 · see citing works
Control of lupus nephritis by changes of gut microbiota
Mu, Q., Zhang, H., Liao, X., Lin, K., Liu, H., Edwards, M. R., Ahmed, S. A., Yuan, R., Li, L., Cecere, T. E., et al. (2017) · Microbiome · doi:10.1186/s40168-017-0300-8 · Cited by 408 · see citing works
Biology of interleukin-22
Wolk, K., Witte, E., Witte, K., Warszawska, K., & Sabat, R. (2010) · Seminars in Immunopathology · doi:10.1007/s00281-009-0188-x · Cited by 395 · see citing works
Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective
Weaver, C. T., & Hatton, R. D. (2009) · Nature reviews. Immunology · doi:10.1038/nri2660 · Cited by 396 · see citing works
CD4 T Helper Cell Subsets and Related Human Immunological Disorders
Zhu, X., & Zhu, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218011 · Cited by 380 · see citing works
Protumor vs Antitumor Functions of IL-17
Murugaiyan, G., & Saha, B. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901017 · Cited by 369 · see citing works
Iron in infection and immunity
Nairz, M., & Weiss, G. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100864 · Cited by 359 · see citing works
MicroRNA-mediated regulation of T helper cell differentiation and plasticity
Baumjohann, D., & Ansel, K. M. (2013) · Nature reviews. Immunology · doi:10.1038/nri3494 · Cited by 354 · see citing works
Heterogeneity of CD4+ memory T cells: Functional modules for tailored immunity
Sallusto, F., & Lanzavecchia, A. (2009) · European Journal of Immunology · doi:10.1002/eji.200939722 · Cited by 348 · see citing works
T Helper Cell Differentiation, Heterogeneity, and PlasticityPreprint
Zhu, J. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a030338 · Cited by 352 · see citing works
Transforming Growth Factor-β-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis
Fabregat, I., & Caballero‐Díaz, D. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00357 · Cited by 352 · see citing works
Heterogeneity of Human CD4 + T Cells Against Microbes
Sallusto, F. (2016) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112056 · Cited by 336 · see citing works
Dry Eye as a Mucosal Autoimmune Disease
Stern, M. E., Schaumburg, C. S., & Pflugfelder, S. C. (2013) · International Reviews of Immunology · doi:10.3109/08830185.2012.748052 · Cited by 344 · see citing works
Discovery and mechanism of ustekinumab
Benson, J., Peritt, D., Scallon, B. J., Heavner, G. A., Shealy, D. J., Giles-Komar, J. M., & Mascelli, M. A. (2011) · mAbs · doi:10.4161/mabs.3.6.17815 · Cited by 345 · see citing works
Interferons Direct Th2 Cell Reprogramming to Generate a Stable GATA-3+T-bet+ Cell Subset with Combined Th2 and Th1 Cell Functions
Hegazy, A. N., Peine, C., Helmstetter, C., Panse, I., Fröhlich, A., Bergthaler, A., Flatz, L., Pinschewer, D. D., Radbruch, A., & Löhning, M. (2010) · Immunity · doi:10.1016/j.immuni.2009.12.004 · Cited by 341 · see citing works
Smad2 and Smad3 Are Redundantly Essential for the TGF-β–Mediated Regulation of Regulatory T Plasticity and Th1 Development
Takimoto, T., Wakabayashi, Y., Sekiya, T., Inoue, N., Morita, R., Ichiyama, K., Takahashi, R., Asakawa, M., Muto, G., Mori, T., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0904100 · Cited by 339 · see citing works
The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4
Ranzani, V., Rossetti, G., Panzeri, I., Arrigoni, A., Bonnal, R. J. P., Curti, S., Gruarin, P., Provasi, E., Sugliano, E., Marconi, M., et al. (2015) · Nature Immunology · doi:10.1038/ni.3093 · Cited by 332 · see citing works
Polyfunctional responses by human T cells result from sequential release of cytokines
Han, Q., Bagheri, N., Bradshaw, E. M., Hafler, D. A., Lauffenburger, D. A., & Love, J. C. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117194109 · Cited by 329 · see citing works
Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease
Coskun, M., Salem, M. A., Pedersen, J., & Nielsen, O. H. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.06.007 · Cited by 327 · see citing works
Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFβ enhance the efficacy of cancer immunotherapy
Ravi, R., Noonan, K. A., Pham, V., Bedi, R., Zhavoronkov, A., Ozerov, I. V., Makarev, E., V. Artemov, A., Wysocki, P. T., Mehra, R., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02696-6 · Cited by 325 · see citing works
Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome: A Paradigm of Immunodeficiency with Autoimmunity
Barzaghi, F., Passerini, L., & Bacchetta, R. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00211 · Cited by 323 · see citing works
Reactive Oxygen Species: Involvement in T Cell Signaling and Metabolism
Franchina, D. G., Dostert, C., & Brenner, D. (2018) · Trends in Immunology · doi:10.1016/j.it.2018.01.005 · Cited by 322 · see citing works
Discrete Roles of STAT4 and STAT6 Transcription Factors in Tuning Epigenetic Modifications and Transcription during T Helper Cell Differentiation
Wei, L., Vahedi, G., Sun, H., Watford, W. T., Takatori, H., Ramos, H. L., Takahashi, H., Liang, J. Z., Gutierrez-Cruz, G., Zang, C., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.06.003 · Cited by 322 · see citing works
The S1P1-mTOR axis directs the reciprocal differentiation of TH1 and Treg cells
Liu, G., Yang, K., Burns, S., Shrestha, S., & Chi, H. (2010) · Nature Immunology · doi:10.1038/ni.1939 · Cited by 322 · see citing works
Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma
Irvin, C., Zafar, I., Good, J. T., Rollins, D. R., Christianson, C. A., Gorska, M. M., Martin, R. J., & Alam, R. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.05.038 · Cited by 318 · see citing works
Bovine cryptosporidiosis: impact, host-parasite interaction and control strategies
Thomson, S., Hamilton, C. A., Hope, J. C., Katzer, F., Mabbott, N. A., Morrison, L. J., & Innes, E. A. (2017) · Veterinary Research · doi:10.1186/s13567-017-0447-0 · Cited by 315 · see citing works
Molecular mechanisms that control the expression and activity of Bcl-6 in TH1 cells to regulate flexibility with a TFH-like gene profile
Oestreich, K. J., Mohn, S. E., & Weinmann, A. S. (2012) · Nature Immunology · doi:10.1038/ni.2242 · Cited by 314 · see citing works
Tumor microenvironments direct the recruitment and expansion of human Th17 cells
Su, X., Ye, J., Hsueh, E. C., Zhang, Y., Hoft, D. F., & Peng, G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902813 · Cited by 324 · see citing works
Plasticity of Human CD4 T Cell Subsets
Geginat, J., Paroni, M., Maglie, S., Alfen, J. S., Kastirr, I., Gruarin, P., Simone, M. C. D., Pagani, M., & Abrignani, S. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00630 · Cited by 289 · see citing works
ATP Inhibits the Generation and Function of Regulatory T Cells Through the Activation of Purinergic P2X Receptors
Schenk, U., Frascoli, M., Proietti, M., Geffers, R., Traggiai, E., Buer, J., Ricordi, C., Westendorf, A. M., & Grassi, F. (2011) · Science Signaling · doi:10.1126/scisignal.2001270 · Cited by 286 · see citing works
The functional plasticity of T cell subsets
Bluestone, J. A., Mackay, C. R., O’Shea, J. J., & Stockinger, B. (2009) · Nature reviews. Immunology · doi:10.1038/nri2654 · Cited by 285 · see citing works
TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells
Takahashi, H., Kanno, T., Nakayamada, S., Hirahara, K., Sciumè, G., Muljo, S. A., Kuchen, S., Casellas, R. C., Wei, L., Kanno, Y., et al. (2012) · Nature Immunology · doi:10.1038/ni.2286 · Cited by 281 · see citing works
Different routes of bacterial infection induce long-lived TH1 memory cells and short-lived TH17 cells
Pepper, M., Linehan, J. L., Pagán, A. J., Zell, T., Dileepan, T., Cleary, P. P., & Jenkins, M. K. (2009) · Nature Immunology · doi:10.1038/ni.1826 · Cited by 279 · see citing works
In Vivo Regulation of Bcl6 and T Follicular Helper Cell Development
Poholek, A. C., Hansen, K., Hernandez, S. G., Eto, D. S., Chandele, A., Weinstein, J. S., Dong, X., Odegard, J., Kaech, S. M., Dent, A. L., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0904023 · Cited by 279 · see citing works
Peripherally Induced Tregs – Role in Immune Homeostasis and Autoimmunity
Yadav, M., Stephan, S. R., & Bluestone, J. A. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00232 · Cited by 274 · see citing works
Cellular and molecular mechanisms of intestinal fibrosis
Speca, S. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i28.3635 · Cited by 274 · see citing works
Cytokines in Autoimmunity: Role in Induction, Regulation, and Treatment
Moudgil, K. D., & Choubey, D. (2011) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2011.0065 · Cited by 269 · see citing works
Therapeutic advances of targeting receptor tyrosine kinases in cancer
Tomuleasa, C., Tigu, A.-B., Munteanu, R. A., Moldovan, C. S., Kegyes, D., Onaciu, A., Gulei, D., Ghiaur, G., Einsele, H., & Croce, C. M. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01899-w · Cited by 279 · see citing works
High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets
Wang, C., Sanders, C. M., Yang, Q., Schroeder, H. W., Wang, E., Babrzadeh, F., Gharizadeh, B., Myers, R., Hudson, J. R., Davis, R. W., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913939107 · Cited by 264 · see citing works
TGF-β: the sword, the wand, and the shield of FOXP3+ regulatory T cells
Tran, D. Q. (2011) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjr033 · Cited by 265 · see citing works
Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism
Zanin-Zhorov, A., Weiss, J. M., Nyuydzefe, M. S., Chen, W., Scher, J. U., Mo, R., Depoil, D., Rao, N., Liu, B., Wei, J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414189111 · Cited by 262 · see citing works
Vitamin A and retinoic acid in T cell-related immunity
Ross, A. C. (2012) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.034637 · Cited by 261 · see citing works
Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies
Cho, J. H., & Feldman, M. A. (2015) · Nature Medicine · doi:10.1038/nm.3897 · Cited by 259 · see citing works
IL-17 and Th17 Cells in Atherosclerosis
Taleb, S., Tedgui, A., & Mallat, Z. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303567 · Cited by 263 · see citing works
Functional and Epigenetic Studies Reveal Multistep Differentiation and Plasticity of In Vitro-Generated and In Vivo-Derived Follicular T Helper Cells
Lu, K. T., Kanno, Y., Cannons, J. L., Handon, R., Bible, P. W., Elkahloun, A. G., Anderson, S. M., Wei, L., Sun, H., O’Shea, J. J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.07.015 · Cited by 259 · see citing works

Authors: Zhou, L., Chong, M. M. W., & Littman, D. R.
Affiliations: Howard Hughes Medical Institute (US)
New York University (US)
Corresponding author: Littman, Dan R.
ORCID: Zhou, Liang
Chong, Mark M.W.
Littman, Dan R.
Venue: Immunity
Publisher: Elsevier BV
Published: 2009-05
Volume: 30
Issue: 5
Pages: 646-655
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2009.05.001
OpenAlex: W2016827757
Cited by: 1,551
References: 101
Citations by year: 2026: 33 · 2025: 48 · 2024: 51 · 2023: 61 · 2022: 73 · 2021: 96 · 2020: 73 · 2019: 61 · 2018: 68 · 2017: 77 · 2016: 90 · 2015: 99 · 2014: 110 · 2013: 145 · 2012: 134
FWCI: 11.46
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1574 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords: CD4+ T cell differentiation, T cell plasticity, Th1 cells, Th2 cells, induced regulatory T cells, Th17 cells, Foxp3, IL-17, T helper cell subsets
MeSH terms: Animals, Cell Differentiation, T-Lymphocytes, Helper-Inducer, Humans, T-Lymphocyte Subsets, Cytokines, Cell Lineage, T-Lymphocytes, Regulatory, Forkhead Transcription Factors

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Plasticity of CD4+ T Cell Lineage Differentiation

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