T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells
Open accessAbstract
Differentiation of naive CD4 + T cells into IFN-γ-producing T helper 1 (T H 1) cells is pivotal for protective immune responses against intracellular pathogens. T-bet, a recently discovered member of the T-box transcription factor family, has been reported to play a critical role in this process, promoting IFN-γ production. Although terminal T H 1 differentiation occurs over days, we now show that challenge of mice with a prototypical T H 1-inducing stimulus, Toxoplasma gondii soluble extract, rapidly induced IFN-γ and T-bet; T-bet induction was substantially lower in IFN-γ-deficient mice. Naive T cells expressed little T-bet, but this transcription factor was induced markedly by the combination of IFN-γ and cognate antigen. Human myeloid antigen-presenting cells showed T-bet induction after IFN-γ stimulation alone, and this induction was antagonized by IL-4 and granulocyte/macrophage colony-stimulating factor. Although T-bet was induced rapidly and directly by IFN-γ, it was not induced by IFN-α, lipopolysaccharide, or IL-1, indicating that this action of IFN-γ was specific. Moreover, T-bet induction was dependent on Stat1 but not Stat4. These data argue for a model in which IFN-γ gene regulation involves an autocrine loop, whereby the cytokine regulates a transcription factor that promotes its own production. These findings substantially alter the current view of T-bet in IFN-γ regulation and promotion of cell-mediated immune responses.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Priming of Th1 cells by IL-12 and IFN-γ results in expression of the master transcription factor T-bet.
“Priming of Th1 cells by IL-12 [188] and IFN-γ [189] results in expression of their master transcription factor T-bet [190]”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [189]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Functional diversity of helper T lymphocytes
Abbas, A. K., MURPHY, K. M. M., & Sher, A. (1996) · Nature · doi:10.1038/383787a0 · Cited by 4,383 · see citing works
Self-citationA Novel Transcription Factor, T-bet, Directs Th1 Lineage Commitment
Szabo, S. J., Kim, S. T., Costa, G. L., Zhang, X., Fathman, C. G., & Glimcher, L. H. (2000) · Cell · doi:10.1016/s0092-8674(00)80702-3 · Cited by 3,589 · see citing works
Zheng, W.-P., & Flavell, R. A. (1997) · Cell · doi:10.1016/s0092-8674(00)80240-8 · Cited by 2,384 · see citing works
Stat6 Is Required for Mediating Responses to IL-4 and for the Development of Th2 Cells
Kaplan, M. H., Schindler, U., Smiley, S. T., & Grusby, M. J. (1996) · Immunity · doi:10.1016/s1074-7613(00)80439-2 · Cited by 1,629 · see citing works
Essential role of Stat6 in IL-4 signalling
Takeda, K., Tanaka, T., Shi, W., Matsumoto, M., Minami, M., Kashiwamura, S.-I., Nakanishi, K., Yoshida, N., Kishimoto, T., & Akira, S. (1996) · Nature · doi:10.1038/380627a0 · Cited by 1,557 · see citing works
Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene
Shimoda, K., van Deursent, J., Sangster, M. Y., Sarawar, S. R., Carson, R. T., Tripp, R. A., Chu, C., Quelle, F. W., Nosaka, T., Vignali, D. A. A., et al. (1996) · Nature · doi:10.1038/380630a0 · Cited by 1,278 · see citing works
Self-citationImpaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice
Kaplan, M. H., Sun, Y.-L., Hoey, T., & Grusby, M. J. (1996) · Nature · doi:10.1038/382174a0 · Cited by 1,240 · see citing works
Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells
Thierfelder, W. E., van Deursen, J. M., Yamamoto, K., Tripp, R. A., Sarawar, S. R., Carson, R. T., Sangster, M. Y., Vignali, D. A. A., Doherty, P. C., Grosveld, G. C., et al. (1996) · Nature · doi:10.1038/382171a0 · Cited by 1,181 · see citing works
Dendritic cell regulation of TH1-TH2 development
Moser, M., & MURPHY, K. M. M. (2000) · Nature Immunology · doi:10.1038/79734 · Cited by 1,106 · see citing works
Seder, R. A., Paul, W. E., Davis, M. M., & Groth, B. F. D. S. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.4.1091 · Cited by 994 · see citing works
Self-citationSousa, C. R. E., Hieny, S. E., Scharton‐Kersten, T., Jankovic, D. L., Charest, H., Germain, R. N., & Sher, A. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.11.1819 · Cited by 911 · see citing works
Self-citationRole 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
Inhibition of Th1 Development Mediated by GATA-3 through an IL-4-Independent Mechanism
Ouyang, W., Ranganath, S. H., Weindel, K., Bhattacharya, D., Murphy, T. L., Sha, W. C., & MURPHY, K. M. M. (1998) · Immunity · doi:10.1016/s1074-7613(00)80671-8 · Cited by 778 · see citing works
Signaling and Transcription in T Helper Development
MURPHY, K. M. M., Ouyang, W., Farrar, J. D., Yang, J., Ranganath, S. H., Asnagli, H., Afkarian, M., & Murphy, T. L. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.451 · Cited by 627 · 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
IFN-γ production by antigen-presenting cells: mechanisms emerge
Frucht, D. M., Fukao, T., Bogdan, C., Schindler, H., O’Shea, J. J., & Koyasu, S. (2001) · Trends in Immunology · doi:10.1016/s1471-4906(01)02005-1 · Cited by 462 · see citing works
Self-citationInterleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes.
Bacon, C. M., Petricoin, E. F., Ortaldo, J. R., Rees, R. C., Larner, A. C., Johnston, J. A., & O’Shea, J. J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7307 · Cited by 449 · see citing works
Self-citationItoh, Y., & Germain, R. N. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.5.757 · Cited by 213 · see citing works
Schindler, H., Lutz, M. B., Röllinghoff, M., & Bogdan, C. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.5.3075 · Cited by 200 · see citing works
Fukao, T., Frucht, D. M., Yap, G. S., Gadina, M., O’Shea, J. J., & Koyasu, S. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.7.4446 · Cited by 199 · see citing works
Self-citationFrucht, D. M., Aringer, M., Galon, J., Danning, C. L., Brown, M., Fan, S., Centola, M. B., Wu, C. Y., Yamada, N., El-Gabalawy, H. S., et al. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.9.4659 · Cited by 196 · see citing works
Self-citationType 1 IFNs and regulation of TH1 responses: enigmas both resolved and emerge
O’Shea, J. J., & Visconti, R. (2000) · Nature Immunology · doi:10.1038/76872 · Cited by 63 · see citing works
Self-citationRegulation of Interleukin-12 Signalling During T Helper Phenotype Development
Jacobson, N. G., Szabo, S. J., Guler, M. L., Gorham, J. D., & MURPHY, K. M. M. (1996) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-5855-2_9 · Cited by 33 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [12]Zheng W, Flavell R A. Cell. 1997;89:587–596. [Google Scholar]
- [13]Szabo S J, Kim S T, Costa G L, Zhang X, Fathman C G, Glimcher L H. Cell. 2000;100:655–669. [Google Scholar]
Cited by
Sorted by citations
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
Interleukin-12 and the regulation of innate resistance and adaptive immunity
Trinchieri, G. (2003) · Nature reviews. Immunology · doi:10.1038/nri1001 · Cited by 3,933 · see citing works
Differentiation of Effector CD4 T Cell Populations
Zhu, J., Yamane, H., & Paul, W. E. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101212 · Cited by 3,452 · see citing works
Self-citationCD4 T cells: fates, functions, and faults
Zhu, J., & Paul, W. E. (2008) · Blood · doi:10.1182/blood-2008-05-078154 · Cited by 1,796 · see citing works
Self-citationThe lineage decisions of helper T cells
MURPHY, K. M. M., & Reiner, S. L. (2002) · Nature reviews. Immunology · doi:10.1038/nri954 · Cited by 1,675 · see citing works
Regulation of Interferon‐γ During Innate and Adaptive Immune Responses
Schoenborn, J. R., & Wilson, C. B. (2007) · Advances in immunology · doi:10.1016/s0065-2776(07)96002-2 · Cited by 1,659 · see citing works
CD4 <sup>+</sup> T Cells: Differentiation and Functions
Luckheeram, R. V., Zhou, R., Verma, A. D., & Xia, B. (2012) · Clinical and Developmental Immunology · doi:10.1155/2012/925135 · Cited by 1,381 · 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 1,341 · see citing works
Self-citationInterferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion
Castro, F., Cardoso, A. P., Gonçalves, R. M., Serre, K., & Oliveira, M. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00847 · Cited by 1,224 · see citing works
O’Shea, J. J., Gadina, M., & Schreiber, R. D. (2002) · Cell · doi:10.1016/s0092-8674(02)00701-8 · Cited by 1,119 · see citing works
Self-citationT-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
Molecular Mechanisms RegulatinG Th1 Immune Responses
Szabo, S. J., Sullivan, B. M., Peng, S. L., & Glimcher, L. H. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.140942 · Cited by 1,021 · 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
Asymmetric T Lymphocyte Division in the Initiation of Adaptive Immune Responses
Chang, J. T., Palanivel, V., Kinjyo, I., Schambach, F., Intlekofer, A. M., Banerjee, A., Longworth, S. A., Vinup, K. E., Mrass, P., Oliaro, J., et al. (2007) · Science · doi:10.1126/science.1139393 · Cited by 845 · see citing works
T-bet Regulates the Terminal Maturation and Homeostasis of NK and Vα14i NKT Cells
Townsend, M. J., Weinmann, A. S., Matsuda, J. L., Salomon, R., Farnham, P., Biron, C. A., Gapin, L., & Glimcher, L. H. (2004) · Immunity · doi:10.1016/s1074-7613(04)00076-7 · Cited by 722 · see citing works
Cytokines in Cancer Immunotherapy
Lee, S. Y., & Margolin, K. A. (2011) · Cancers · doi:10.3390/cancers3043856 · Cited by 695 · see citing works
O’Shea, J. J., Ma, A. I., & Lipsky, P. E. (2002) · Nature reviews. Immunology · doi:10.1038/nri702 · Cited by 677 · see citing works
Self-citationLonghi, M. P., Trumpfheller, C., Idoyaga, J., Caskey, M. F., de Matos, I. G., Kluger, C., Salazar, A. Μ., Colonna, M., & Steinman, R. M. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090247 · Cited by 663 · see citing works
Modulation of Innate and Adaptive Immune Responses by Tofacitinib (CP-690,550)
Ghoreschi, K., Jesson, M. I., Xiong, L., Lee, J. L., Ghosh, S., Alsup, J. W., Warner, J. D., Tanaka, M., Steward-Tharp, S. M., Gadina, M., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003668 · Cited by 642 · see citing works
Self-citationInterferon-gamma (IFN-γ): Exploring its implications in infectious diseases
Kak, G., Raza, M., & Tiwari, B. K. (2018) · BioMolecular Concepts · doi:10.1515/bmc-2018-0007 · Cited by 624 · see citing works
The role of Th1/Th2 polarization in mucosal immunity
Neurath, M. F., Finotto, S., & Glimcher, L. H. (2002) · Nature Medicine · doi:10.1038/nm0602-567 · Cited by 623 · see citing works
Alspach, E., Lussier, D. M., & Schreiber, R. D. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028480 · Cited by 617 · see citing works
Peripheral CD4+ T‐cell differentiation regulated by networks of cytokines and transcription factors
Zhu, J., & Paul, W. E. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00951.x · Cited by 596 · see citing works
Self-citationTranscriptional Basis of Mouse and Human Dendritic Cell Heterogeneity
Brown, C. C., Gudjonson, H., Pritykin, Y., Deep, D., Lavallée, V., Mendoza, A., Fromme, R. M., Mažutis, L., Ariyan, C. E., Leslie, C. S., et al. (2019) · Cell · doi:10.1016/j.cell.2019.09.035 · Cited by 582 · see citing works
The biology of IL-12: coordinating innate and adaptive immune responses
Watford, W. T., Moriguchi, M., Morinobu, A., & O’Shea, J. J. (2003) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(03)00043-1 · Cited by 578 · see citing works
Self-citationSignaling by IL‐12 and IL‐23 and the immunoregulatory roles of STAT4
Watford, W. T., Hissong, B. D., Bream, J. H., Kanno, Y., Muul, L. M., & O’Shea, J. J. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00211.x · Cited by 570 · see citing works
Self-citationStat3 and Stat4 Direct Development of IL-17-Secreting Th Cells
Mathur, A. N., Chang, H., Zisoulis, D. G., Stritesky, G. L., Yu, Q., O’Malley, J. T., Kapur, R., Levy, D. E., Kansas, G. S., & Kaplan, M. H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.8.4901 · Cited by 548 · 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
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
Bhol, N. K., Bhanjadeo, M. M., Singh, A. K., Dash, U. C., Ojha, R. R., Majhi, S., Duttaroy, A. K., & Jena, A. B. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117177 · Cited by 531 · 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
Cytokines in the Treatment of Cancer
Conlon, K. C., Miljković, M. D., & Waldmann, T. A. (2018) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2018.0019 · Cited by 523 · see citing works
Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand
Solt, L. A., Kumar, N., Nuhant, P., Wang, Y., Lauer, J. L., Liu, J., Istrate, M. A., Kamenecka, T. M., Roush, W. R., Vidović, D., et al. (2011) · Nature · doi:10.1038/nature10075 · Cited by 508 · see citing works
Nguyen, K. B., Watford, W. T., Salomon, R., Hofmann, S. R., Pien, G. C., Morinobu, A., Gadina, M., O’Shea, J. J., & Biron, C. A. (2002) · Science · doi:10.1126/science.1074900 · Cited by 495 · see citing works
Self-citationT-bet: a bridge between innate and adaptive immunity
Lazarevic, V., Glimcher, L. H., & Lord, G. M. (2013) · Nature Reviews Immunology · doi:10.1038/nri3536 · Cited by 486 · see citing works
Loss of T-bet, But Not STAT1, Prevents the Development of Experimental Autoimmune Encephalomyelitis
Bettelli, E., Sullivan, B., Szabo, S. J., Sobel, R., Glimcher, L., & Kuchroo, V. (2004) · Journal of Experimental Medicine · doi:10.1084/jem.20031819 · Cited by 546 · see citing works
The IL-27R (WSX-1) Is Required to Suppress T Cell Hyperactivity during Infection
Villarino, A. V., Hibbert, L., Lieberman, L. A., Wilson, E. H., Mak, T. W., Yoshida, H., Kastelein, R. A., Saris, C. J. M., & Hunter, C. A. (2003) · Immunity · doi:10.1016/s1074-7613(03)00300-5 · Cited by 484 · see citing works
Regulation of antiviral T cell responses by type I interferons
Crouse, J., Kalinke, U., & Oxenius, A. (2015) · Nature reviews. Immunology · doi:10.1038/nri3806 · Cited by 480 · see citing works
Zhu, J., Yamane, H., Cote-Sierra, J., Guo, L.-Y., & Paul, W. (2006) · Cell Research · doi:10.1038/sj.cr.7310002 · Cited by 497 · see citing works
Self-citationLucas, 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
The PDL1-PD1 Axis Converts Human T H 1 Cells into Regulatory T Cells
Amarnath, S., Mangus, C. W., Wang, J. C. M., Wei, F., He, A., Kapoor, V., Foley, J., Massey, P. R., Felizardo, T. C., Riley, J. L., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3003130 · Cited by 448 · see citing works
Liao, W., Lin, J.-X., Wang, L., Li, P., & Leonard, W. J. (2011) · Nature Immunology · doi:10.1038/ni.2030 · Cited by 474 · see citing works
Antigen-driven effector CD8 T cell function regulated by T-bet
Sullivan, B. M., Juedes, A. E., Szabo, S. J., von Herrath, M., & Glimcher, L. H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2636938100 · Cited by 439 · see citing works
Antigen presentation by dendritic cells and their instruction of CD4+ T helper cell responses
Hilligan, K. L., & Ronchese, F. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0465-0 · Cited by 433 · 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
Early Th1 Cell Differentiation Is Marked by a Tfh Cell-like Transition
Nakayamada, S., Kanno, Y., Takahashi, H., Jankovic, D. L., Lu, K. T., Johnson, T. A., Sun, H., Vahedi, G., Hakim, O., Handon, R., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.11.012 · Cited by 411 · see citing works
Self-citationTh17 Cell, the New Player of Neuroinflammatory Process in Multiple Sclerosis
Jadidi‐Niaragh, F., & Mirshafiey, A. (2011) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2011.02536.x · Cited by 389 · see citing works
Pathogenesis of allergic diseases and implications for therapeutic interventions
Wang, J., Zhou, Y., Zhang, H., Hu, L., Liu, J., Wang, L., Wang, T., Zhang, H., Cong, L., & Wang, Q. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01344-4 · Cited by 415 · see citing works
Interleukin 12 a Key Immunoregulatory Cytokine in Infection Applications
Hamza, T., Barnett, J. B., & Li, B. (2010) · International Journal of Molecular Sciences · doi:10.3390/ijms11030789 · Cited by 383 · see citing works
Agnello, D., Lankford, C. S. R., Bream, J. H., Morinobu, A., Gadina, M., O’Shea, J. J., & Frucht, D. M. (2003) · Journal of Clinical Immunology · doi:10.1023/a:1023381027062 · Cited by 380 · see citing works
Self-citationSTATs Shape the Active Enhancer Landscape of T Cell Populations
Vahedi, G., Takahashi, H., Nakayamada, S., Sun, H., Sartorelli, V., Kanno, Y., & O’Shea, J. J. (2012) · Cell · doi:10.1016/j.cell.2012.09.044 · Cited by 365 · see citing works
Self-citationMicroRNA-29 Regulates T-Box Transcription Factors and Interferon-γ Production in Helper T Cells
Steiner, D. F., Thomas, M. F., Hu, J. K., Yang, Z., Babiarz, J., Allen, C. D. C., Matloubian, M., Blelloch, R. H., & Ansel, K. M. (2011) · Immunity · doi:10.1016/j.immuni.2011.07.009 · Cited by 365 · 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
Takemoto, N., Intlekofer, A. M., Northrup, J. T., Wherry, E. J., & Reiner, S. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.11.7515 · Cited by 339 · see citing works
Usui, T., Preiß, J., Kanno, Y., Yao, Z. J., Bream, J. H., O’Shea, J. J., & Strober, W. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052165 · Cited by 337 · see citing works
Self-citationZhu, J., Jankovic, D., Oler, A. J., Wei, G., Sharma, S., Hu, G., Guo, L., Yagi, R., Yamane, H., Punkosdy, G., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.09.007 · Cited by 335 · see citing works
Self-citationGreen, A. M., DiFazio, R. M., & Flynn, J. L. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200061 · Cited by 330 · see citing works
Th1 and Th17 Cells in Tuberculosis: Protection, Pathology, and Biomarkers
Lyadova, I. V., & Panteleev, A. V. (2015) · Mediators of Inflammation · doi:10.1155/2015/854507 · Cited by 329 · see citing works
Meier, W. A., Galeota, J. A., Osorio, F. A., Husmann, R. J., Schnitzlein, W. M., & Zuckermann, F. A. (2003) · Virology · doi:10.1016/s0042-6822(03)00009-6 · Cited by 325 · see citing works
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
Self-citationJasper, M. J. (2006) · Molecular Human Reproduction · doi:10.1093/molehr/gal032 · Cited by 319 · see citing works
IL-27 and IFN- α Signal via Stat1 and Stat3 and Induce T-Bet and IL-12R β 2 in Naive T Cells
Hibbert, L., Pflanz, S., Malefyt, R. D. W., & Kastelein, R. A. (2003) · Journal of Interferon & Cytokine Research · doi:10.1089/10799900360708632 · Cited by 318 · see citing works
Hlx is induced by and genetically interacts with T-bet to promote heritable TH1 gene induction
Mullen, A. C., Hutchins, A. S., High, F. A., Lee, H. W., Sykes, K. J., Chodosh, L. A., & Reiner, S. L. (2002) · Nature Immunology · doi:10.1038/ni807 · Cited by 306 · see citing works
Rubtsova, K., Rubtsov, A. V., van Dyk, L. F., Kappler, J. W., & Marrack, P. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312348110 · Cited by 300 · see citing works
Recent developments in the transcriptional regulation of cytolytic effector cells
Glimcher, L. H., Townsend, M. J., Sullivan, B. M., & Lord, G. M. (2004) · Nature reviews. Immunology · doi:10.1038/nri1490 · Cited by 293 · see citing works
CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells
Liu, N., Ohnishi, N., Ni, L., Akira, S., & Bacon, K. B. (2003) · Nature Immunology · doi:10.1038/ni941 · Cited by 291 · see citing works
Usui, T., Nishikomori, R., Kitani, A., & Strober, W. (2003) · Immunity · doi:10.1016/s1074-7613(03)00057-8 · Cited by 287 · see citing works
Schulz, E. G., Mariani, L., Radbruch, A., & Höfer, T. (2009) · Immunity · doi:10.1016/j.immuni.2009.03.013 · Cited by 280 · see citing works
Lugo‐Villarino, G., Maldonado-López, R., Possemato, R., Peñaranda, C., & Glimcher, L. H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1332767100 · Cited by 269 · see citing works
T-bet is required for optimal proinflammatory CD4+ T-cell trafficking
Lord, G. M. (2005) · Blood · doi:10.1182/blood-2005-04-1393 · Cited by 270 · see citing works
A method for the generation of standardized qualitative dynamical systems of regulatory networks
Mendoza, L., & Xénarios, I. (2006) · Theoretical Biology and Medical Modelling · doi:10.1186/1742-4682-3-13 · Cited by 265 · see citing works
T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17
Rangachari, M., Mauermann, N., Marty, R. R., Dirnhofer, S., Kurrer, M. O., Komnenovic, V., Penninger, J. M., & Eriksson, U. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052222 · Cited by 264 · see citing works
Interleukin‐35: odd one out or part of the family?
Collison, L. W., & Vignali, D. A. A. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00704.x · Cited by 262 · see citing works
Hirahara, K., Ghoreschi, K., Yang, X., Takahashi, H., Laurence, A. D. J., Vahedi, G., Sciumè, G., Hall, A. O., Dupont, C. D., Francisco, L. M., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.03.024 · Cited by 253 · see citing works
Self-citationMicro‐RNA‐155 inhibits IFN‐γ signaling in CD4 + T cells
Banerjee, A., Schambach, F., DeJong, C. S., Hammond, S. M., & Reiner, S. L. (2009) · European Journal of Immunology · doi:10.1002/eji.200939381 · Cited by 252 · see citing works
IL-21 Up-Regulates the Expression of Genes Associated with Innate Immunity and Th1 Response
Strengell, M., Sareneva, T., Foster, D., Julkunen, I., & Matikainen, S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.7.3600 · Cited by 249 · see citing works
Lazarevic, V., & Glimcher, L. H. (2011) · Nature Immunology · doi:10.1038/ni.2059 · Cited by 248 · see citing works
The host immune response to gastrointestinal nematode infection in sheep
McRae, K. M., Stear, M. J., Good, B., & Keane, O. M. (2015) · Parasite Immunology · doi:10.1111/pim.12290 · Cited by 244 · see citing works
An epigenetic silencing pathway controlling T helper 2 cell lineage commitment
Allan, R. S., Zueva, E., Cammas, F. M., Schreiber, H. A., Masson, V., Belz, G. T., Roche, D. M. J., Maison, C., Quivy, J., Almouzni, G., et al. (2012) · Nature · doi:10.1038/nature11173 · Cited by 239 · see citing works
The Transcription Factor STAT3 Is Required for T Helper 2 Cell Development
Stritesky, G. L., Muthukrishnan, R., Sehra, S., Goswami, R., Pham, D., Travers, J. B., Nguyen, E., Levy, D. E., & Kaplan, M. H. (2011) · Immunity · doi:10.1016/j.immuni.2010.12.013 · Cited by 234 · see citing works
Ho, I., & Glimcher, L. H. (2002) · Cell · doi:10.1016/s0092-8674(02)00705-5 · Cited by 233 · see citing works
Understanding the Pro- and Anti-Inflammatory Properties of IL-27
Villarino, A. V., Huang, E., & Hunter, C. A. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.2.715 · Cited by 233 · see citing works
Nishihara, M., Ogura, H., Ueda, N., Tsuruoka, M., Kitabayashi, C., Tsuji, F., Aono, H., Ishihara, K., Huseby, E., Betz, U. A. K., et al. (2007) · International Immunology · doi:10.1093/intimm/dxm045 · Cited by 268 · see citing works
Thieu, V. T., Yu, Q., Chang, H., Yeh, N., Nguyen, E., Sehra, S., & Kaplan, M. H. (2008) · Immunity · doi:10.1016/j.immuni.2008.08.017 · Cited by 231 · 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
Self-citationHow Diverse--CD4 Effector T Cells and their Functions
Wan, Y. Y., & Flavell, R. A. (2009) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjp001 · Cited by 221 · see citing works
Th1/Th2 Cell Differentiation and Molecular Signals
Zhang, Y., Zhang, Y., Gu, W., & Sun, B. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-94-017-9487-9_2 · Cited by 223 · see citing works
Kamiya, S., Owaki, T., Morishima, N., Fukai, F., Mizuguchi, J., & Yoshimoto, T. (2004) · Journal of Immunology · doi:10.4049/jimmunol.173.6.3871 · Cited by 248 · see citing works
Series Introduction: JAK-STAT signaling in human disease
Schindler, C. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15644 · Cited by 217 · see citing works
Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction
Furumoto, Y., Smith, C. K., Blanco, L. P., Zhao, W., Brooks, S. R., Thacker, S. G., Zarzour, A., Sciumè, G., Tsai, W. L., Trier, A. M., et al. (2016) · Arthritis & Rheumatology · doi:10.1002/art.39818 · Cited by 217 · see citing works
Self-citationIL-27 Limits IL-2 Production during Th1 Differentiation
Villarino, A. V., Stumhofer, J. S., Saris, C. J. M., Kastelein, R. A., de Sauvage, F. J., & Hunter, C. A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.1.237 · Cited by 216 · see citing works
Roles of interferon-regulatory factors in T-helper-cell differentiation
Lohoff, M. D., & Mak, T. W. (2005) · Nature reviews. Immunology · doi:10.1038/nri1552 · Cited by 214 · see citing works
A unique role for IL-23 in promoting cellular immunity
Lankford, C. S. R., & Frucht, D. M. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0602326 · Cited by 211 · see citing works
Self-citationPolarized immune responses differentially regulate cancer development
Johansson, M., DeNardo, D. G., & Coussens, L. M. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00600.x · Cited by 209 · see citing works
Morinobu, A., Gadina, M., Strober, W., Visconti, R., Fornace, A. J., Montagna, C., Feldman, G. M., Nishikomori, R., & O’Shea, J. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182618999 · Cited by 207 · see citing works
Self-citationGene Silencing Quantitatively Controls the Function of a Developmental trans-Activator
Hutchins, A. S., Mullen, A. C., Lee, H. W., Sykes, K. J., High, F. A., Hendrich, B., Bird, A. P., & Reiner, S. L. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00564-6 · Cited by 206 · see citing works
Arsenio, J., Kakaradov, B., Metz, P. J., Kim, S. H., Yeo, G. W., & Chang, J. T. (2014) · Nature Immunology · doi:10.1038/ni.2842 · Cited by 210 · see citing works
A Role for IL-27 in Early Regulation of Th1 Differentiation
Owaki, T., Asakawa, M., Morishima, N., Hata, K., Fukai, F., Matsui, M., Mizuguchi, J., & Yoshimoto, T. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.4.2191 · Cited by 205 · see citing works
Further Checkpoints in Th1 Development
Robinson, D. S., & O’Garra, A. (2002) · Immunity · doi:10.1016/s1074-7613(02)00331-x · Cited by 204 · see citing works
- Authors
- Lighvani, A. A., Frucht, D. M., Jankovic, D., Yamane, H., Aliberti, J., Hissong, B. D., Nguyen, B. V., Gadina, M., Sher, A., Paul, W. E., & O'Shea, J. J.
- Affiliations
- National Institutes of Health (US)
- Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Immunobiology Section, Laboratory of Parasitic Diseases, and Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Cell Biology Laboratory, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
- Corresponding author
- Frucht, David M.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-12-18
- Volume
- 98
- Issue
- 26
- Pages
- 15137-15142
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC64996
- OpenAlex
- W2011754426
- Cited by
- 783
- References
- 23
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 17 · 2023: 30 · 2022: 25 · 2021: 25 · 2020: 23 · 2019: 18 · 2018: 26 · 2017: 20 · 2016: 23 · 2015: 24 · 2014: 43 · 2013: 34 · 2012: 40
- FWCI
- 13.58
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- T-bet, interferon-gamma, Toxoplasma gondii, STAT1, autocrine loop, IL-4, GM-CSF, myeloid antigen-presenting cells, naive CD4+ T cells, T-box transcription factor, cell-mediated immunity
- MeSH terms
- T-bet Transcription Factor, Animals, Antibodies, Monoclonal, Base Sequence, Cell Differentiation, Cells, Cultured, Dendritic Cells, Female, Humans, Interferon-gamma, Macrophages, Mice, Inbred C57BL, Transcription Factors, CD4-Positive T-Lymphocytes, Up-Regulation, DNA Primers, T-Box Domain Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
