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Transcriptional and Epigenetic Control of T Helper Cell Specification: Molecular Mechanisms Underlying Commitment and Plasticity
Open accessAbstract
T helper cell differentiation occurs in the context of the extracellular cytokine milieu evoked by diverse microbes and other pathogenic stimuli along with T cell receptor stimulation. The culmination of these signals results in specification of T helper lineages, which occurs through the combinatorial action of multiple transcription factors that establish distinctive transcriptomes. In this manner, inducible, but constitutively active, master regulators work in conjunction with factors such as the signal transducer and activator of transcriptions (STATs) that sense the extracellular environment. The acquisition of a distinctive transcriptome also depends on chromatin modifications that impact key cis elements as well as the changes in global genomic organization. Thus, signal transduction and epigenetics are linked in these processes of differentiation. In this review, recent advances in understanding T helper lineage specification and deciphering the action of transcription factors are summarized with emphasis on comprehensive views of the dynamic T cell epigenome.
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“Differentiation of T cells to specific TH lineages is driven by specific transcription factors but reinforced by epigenetic modifications on histone tails (H3K4 and H3K27 trimethylation) and DNA methylation of CpG dinucleotides (103).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [103]
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Citations
Cites
Bartel (2004) · doi:10.1016/s0092-8674(04)00045-5 · Cited by 34,714
Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
Lieberman-Aiden, E., van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B. R., Sabo, P. J., Dorschner, M. O., et al. (2009) · Science · doi:10.1126/science.1181369 · Cited by 8,898 · cited 6×
“2011) miRNA expression miRNA-seq miRNA miRNAome Kuchen (Immunity, 2010), Rossi (Nature Immunoloty, 2011) Chromosome conformation 4C-, 5C-, Hi-C-seq Chromatin proximity ligation Chromatin looping, globule, compartment NA Chromatin interaction through DNA binding protein ChIA-PETseq ChIP + chromatin proximity ligation +…”
MethodInfluentialThe ENCODE Project Consortium (2007) · Nature · doi:10.1038/nature05874 · Cited by 5,223 · cited 2×
“The advent of next generation sequencing has provided an “enhancer signaure” to look for, namely monomethylation of histone H3 lysine 4 (H3K4me1) in the absence of trimetylation (H3K4me3) (118-120) and binding of p300 histone acetyltransferase (116, 121-123).”
BackgroundHuman DNA methylomes at base resolution show widespread epigenomic differences
Lister, R., Pelizzola, M., Dowen, R. H., Hawkins, R. D., Hon, G., Tonti-Filippini, J., Nery, J. R., Lee, L., Ye, Z., Ngo, Q.-M., et al. (2009) · Nature · doi:10.1038/nature08514 · Cited by 4,673 · cited 2×
“This method relies on the nature of bisulfite treatment to selectively convert unmethylated cytosine to uracil so that subsequent deep sequencing would distinguish differential methylation status on a given cytosine residue at a single nucleotide resolution (34, 91).”
BackgroundMethodHistone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302
Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., et al. (2009) · Nature · doi:10.1038/nature07672 · Cited by 4,098 · cited 24×
“This paradigm will likely be underscored even more in the near future with the recent introduction of enhancer RNAs (eRNAs)(130) and promoter-associated RNAs (144, 145) to ncRNA repertoire.”
BackgroundInfluentialA Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing
Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., Pfeffer, S., Rice, A., Kamphorst, A. O., Landthaler, M., et al. (2007) · Cell · doi:10.1016/j.cell.2007.04.040 · Cited by 3,626
The Transcriptional Landscape of the Mammalian Genome
Carninci, P., Kasukawa, T., Katayama, S., Gough, J., Frith, M. C., Maeda, N., Oyama, R., Ravasi, T., Lenhard, B., Wells, C. A., et al. (2005) · Science · doi:10.1126/science.1112014 · Cited by 3,492
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 · cited 13×
“Nature Immunology.”
BackgroundMethodInfluentialTet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine
Ito, S., Shen, L., Dai, Q., Wu, S. C., Collins, L. B., Swenberg, J. A., He, C., & Zhang, Y. (2011) · Science · doi:10.1126/science.1210597 · Cited by 3,451 · cited 1×
“This raises the possibility that TET proteins contribute to DNA demethylation reactions (40).”
Background
Research works printed but not linked: 1
- Eyerich S, 2009, J. Clin. Investig., 119, 3573
Cited by
Sorted by citations
Fueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363
JAK and STAT Signaling Molecules in Immunoregulation and Immune-Mediated Disease
O’Shea, J. J., & Plenge, R. M. (2012) · Immunity · doi:10.1016/j.immuni.2012.03.014 · Cited by 1,186
Self-citationThe JAK-STAT pathway at 30: Much learned, much more to do
Philips, R. L., Wang, Y., Cheon, H., Kanno, Y., Gadina, M., Sartorelli, V., Horvath, C. M., Darnell, J. E., Jr., Stark, G. R., & O’Shea, J. J. (2022) · Cell · doi:10.1016/j.cell.2022.09.023 · Cited by 755
Self-citationHillmer, E. J., Zhang, H., Li, H. S., & Watowich, S. S. (2016) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2016.05.001 · Cited by 740
“Collectively, the opposing functions for STAT3 and STAT5 at the transcriptional and epigenetic levels induce distinct developmental outcomes from naïve CD4 T cells, contributing essentially to the diversity of CD4 T cell subsets [200].”
BackgroundTranscriptional 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 601
“Publis This is an open access article under the CC BY license (http://creative feron (IFN)-g-producing Th1 cells, interleukin (IL)-4-producing Th2 cells, and IL-17-producing Th17 cells, respectively (Kanno et al., 2012; Littman and Rudensky, 2010).”
BackgroundMechanisms of Jak/STAT Signaling in Immunity and Disease
Villarino, A. V., Kanno, Y., Ferdinand, J. R., & O’Shea, J. J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401867 · Cited by 564
“In Th cells, thousands of binding sites have been mapped for each family member, sometimes proximal to transcriptional start sites, as would have been predicted, but more often distal, typically associated with enhancers or other cis-regulatory elements (10).”
BackgroundSelf-citationIn Vivo CD4 + T Cell Differentiation and Function: Revisiting the Th1/Th2 Paradigm
Ruterbusch, M., Pruner, K. B., Shehata, L., & Pepper, M. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-103019-085803 · Cited by 550
Zhu, J. (2015) · Cytokine · doi:10.1016/j.cyto.2015.05.010 · Cited by 523
“Transcriptional regulation of Il4/Il13 expression, like transcriptional regulation of any other lineage specific genes, highly depends on chromatin remodeling and epigenetic modifications [17,183,184].”
BackgroundEngineering CAR-T cells: Design concepts
Srivastava, S., & Riddell, S. R. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.06.004 · Cited by 506
“Epigenetic modifications, in the form of changes to DNA and/or histones, are known to play an important role in CD4+ helper T cell differentiation and CD8+ memory formation [80,81].”
BackgroundThe IL-23-IL-17 axis in inflammatory arthritis
Lubberts, E. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.53 · Cited by 442
Walsh, M. C., Lee, J., & Choi, Y. (2015) · Immunological Reviews · doi:10.1111/imr.12302 · Cited by 451
CD4 + T-cell subsets in inflammatory diseases: beyond the T h 1/T h 2 paradigm
Hirahara, K., & Nakayama, T. (2016) · International Immunology · doi:10.1093/intimm/dxw006 · Cited by 417
Self-citationTh2 Cells in Health and Disease
Nakayama, T., Hirahara, K., Onodera, A., Endo, Y., Hosokawa, H., Shinoda, K., Tumes, D. J., & Okamoto, Y. (2016) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052350 · Cited by 412
Self-citationYagi, R., Zhong, C., Northrup, D. L., Yu, F., Bouladoux, N. J., Spencer, S. P., Hu, G., Barron, L., Sharma, S., Nakayama, T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.01.012 · Cited by 380
“CD4 T helper (Th) cells are central in orchestrating adaptive immune responses; distinct Th cell subsets are involved in protective immune responses to a variety of pathogens (Kanno et al., 2012; Zhu et al., 2010).”
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 413
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 363
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
“It has become increasingly clear that T cell differentiation is a complex process orchestrated by several transcription factors that promote expression of lineagespecific genes while inhibiting expression of genes characteristic of different lineages through multiple mechanisms, which include chromatin remodeling even…”
BackgroundRanzani, 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 340
Ichiyama, K., Chen, T., Wang, X., Yan, X., Kim, B.-S., Tanaka, S., Ndiaye-Lobry, D., Deng, Y., Zou, Y., Zheng, P., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.03.005 · Cited by 327
“Th cell differentiation depends on the complex network of cytokine signaling imposed on lineage-specific transcription factors (Kanno et al., 2012).”
Bharadwaj, U., Kasembeli, M. M., Robinson, P., & Tweardy, D. J. (2020) · Pharmacological Reviews · doi:10.1124/pr.119.018440 · Cited by 314
“Naive CD41 T cells, responding to T cell receptor–mediated antigen presentation or other cues, develop into distinct effector subsets with unique functions, including CD81 T cell activation, stimulation of innate immune cells, or induction of B cell responses (Kanno et al., 2012).”
BackgroundPolyamine metabolism is a central determinant of helper T cell lineage fidelity
Puleston, D. J., Baixauli, F., Sanin, D. E., Edwards-Hicks, J., Villa, M., Kabat, A. M., Kamiński, M. M., Stanckzak, M., Weiss, H. J., Grzes, K. M., et al. (2021) · Cell · doi:10.1016/j.cell.2021.06.007 · Cited by 305
“Moreover, maintaining IL-17 synthesis requires inhibition of T-bet expression (Kanno et al., 2012; Lazarevic et al., 2013), but reducing aberrant T-bet levels in Odc / and Dohh / TH17 cells failed to restore IL-17A (Figure S7A).”
BackgroundInfluentialMetabolic and Epigenetic Coordination of T Cell and Macrophage Immunity
Phan, A. T., Goldrath, A. W., & Glass, C. K. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.016 · Cited by 296
“Therefore, regulation of TF binding and activity by the epigenome is a crucial step in modulating differentiation programs and in immune cells can be essential for permitting or inhibiting the execution of gene expression downstream of immune stimuli (Kanno et al., 2012).”
Transcriptional regulation of innate lymphoid cell fate
Serafini, N., Vosshenrich, C. A. J., & Santo, J. P. D. (2015) · Nature reviews. Immunology · doi:10.1038/nri3855 · Cited by 309
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 313
Tumes, D. J., Onodera, A., Suzuki, A., Shinoda, K., Endo, Y., Iwamura, C., Hosokawa, H., Koseki, H., Tokoyoda, K., Suzuki, Y., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.09.012 · Cited by 291
T follicular helper cells in space-time
Qi, H. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.94 · Cited by 281
Plasticity of tumour and immune cells: a source of heterogeneity and a cause for therapy resistance?
Hölzel, M., Bovier, A., & Tüting, T. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3498 · Cited by 275
The liver–brain–gut neural arc maintains the Treg cell niche in the gut
Teratani, T., Mikami, Y., Nakamoto, N., Suzuki, T., Harada, Y., Okabayashi, K., Hagihara, Y., Taniki, N., Kohno, K., Shibata, S., et al. (2020) · Nature · doi:10.1038/s41586-020-2425-3 · Cited by 270
Modulation of EZH2 expression in T cells improves efficacy of anti-CTLA-4 therapy
Goswami, S., Apostolou, I., Zhang, J., Skepner, J., Anandhan, S., Zhang, X., Xiong, L., Trojer, P., Aparicio, A., Subudhi, S. K., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99760 · Cited by 244
Bruno, A., Ferlazzo, G., Albini, A., & Noonan, D. M. (2014) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dju200 · Cited by 182
Escobar, T. M., Kanellopoulou, C., Kugler, D. G., Kilaru, G., Nguyen, C. K., Nagarajan, V., Bhairavabhotla, R., Northrup, D. L., Zahr, R., Burr, P., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.03.014 · Cited by 182
“Transcriptional and epigenetic programs initiated within CD4 T cells promote changes in gene expression, ultimately resulting in production of their signature cytokines (Ciofani et al., 2012; Kanno et al., 2012; Yosef et al., 2013).”
T‐cell subsets in the germinal center
Ramiscal, R. R., & Vinuesa, C. G. (2013) · Immunological Reviews · doi:10.1111/imr.12031 · Cited by 190
“BCL6 expression identifies Tfh cells from other effector CD4 T cells, namely Th1, Th2, Th17, and T-regulatory (Treg) cells, which are instead genetically programmed by the transcription factors Tbet, GATA3, retinoid orphan receptor ct (RORct), and forkhead box protein 3 (FoxP3), respectively (21).”
BackgroundFang, D., & Zhu, J. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20170494 · Cited by 175
“This is also true for T cell differentiation and ILC development (Kanno et al., 2012; Shih et al., 2014).”
BackgroundDissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation
Tsagaratou, A., Äijö, T., Lio, C. J., Yue, X., Huang, Y., Jacobsen, S. E., Lähdesmäki, H. J., & Rao, A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1412327111 · Cited by 186
“Gata3 is necessary for the DP-to-SP transition (40), for Th2 differentiation (22, 24) and for CD8 T-cell homeostasis and proliferation (41, 42).”
BackgroundThe RAG Recombinase Dictates Functional Heterogeneity and Cellular Fitness in Natural Killer Cells
Karo, J. M., Schatz, D. G., & Sun, J. C.-Y. (2014) · Cell · doi:10.1016/j.cell.2014.08.026 · Cited by 171
“passed on to daughter generations (potentially through epigenetic imprinting (Kanno et al., 2012; Weng et al., 2012)).”
Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells
Koues, O. I., Collins, P. L., Cella, M., Robinette, M. L., Porter, S. I., Pyfrom, S., Payton, J. E., Colonna, M., & Oltz, E. M. (2016) · Cell · doi:10.1016/j.cell.2016.04.014 · Cited by 168
Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential
Wang, L., Liang, Y., Zhao, C., Ma, P., Zeng, S., Ju, D., Zhao, M., Yu, M., & Shi, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02326-4 · Cited by 190
IL-21 induces IL-22 production in CD4+ T cells
Yeste, A., Mascanfroni, I. D., Nadeau, M., Burns, E. J., Tukpah, A.-M. C., Santiago, A. F., Wu, C., Patel, B., Kumar, D., & Quintana, F. J. (2014) · Nature Communications · doi:10.1038/ncomms4753 · Cited by 159
Critical role of histone demethylase Jmjd3 in the regulation of CD4+ T-cell differentiation
Li, Q., Zou, J., Wang, M., Ding, X., Chepelev, I., Zhou, X., Zhao, W., Wei, G., Cui, J., Zhao, K., et al. (2014) · Nature Communications · doi:10.1038/ncomms6780 · Cited by 152
Lymph node – an organ for T‐cell activation and pathogen defense
Gasteiger, G., Ataide, M. A., & Kastenmüller, W. (2016) · Immunological Reviews · doi:10.1111/imr.12399 · Cited by 155
“In order to respond in all these different contexts, Treg co-opt functional programs driven by the master transcription factors that specify CD4 T ‘helper’ lineages (175, 176).”
BackgroundEZH2 is crucial for both differentiation of regulatory T cells and T effector cell expansion
Yang, X., Jiang, K., Hirahara, K., Vahedi, G., Afzali, B., Sciumè, G., Bonelli, M. M., Sun, H., Jankovic, D. L., Kanno, Y., et al. (2015) · Scientific Reports · doi:10.1038/srep10643 · Cited by 156
Self-citationNatural killer cells: walking three paths down memory lane
Min‐Oo, G., Kamimura, Y., Hendricks, D. W., Nabekura, T., & Lanier, L. L. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.02.005 · Cited by 149
Epi-drugs in combination with immunotherapy: a new avenue to improve anticancer efficacy
Mazzone, R., Zwergel, C., Mai, A., & Valente, S. (2017) · Clinical Epigenetics · doi:10.1186/s13148-017-0358-y · Cited by 151
“Moreover, CD4 Th subsets are distinguished by their phenotype as well as by the transcription factors that control their differentiation, including T-bet in Th1, GATA-3 in Th2, RAR-related orphan receptor γ (RORγT) in Th17, and forkhead box protein 3 (Foxp3) in Treg [41].”
BackgroundEmbryotoxic cytokines—Potential roles in embryo loss and fetal programming
Robertson, S. A., Chin, P. Y., Femia, J. G., & Brown, H. M. (2017) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2017.12.003 · Cited by 147
Histone deacetylase function in CD4+ T cells
Ellmeier, W., & Seiser, C. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0037-z · Cited by 146
DNA Methylation in Systemic Lupus Erythematosus
Hedrich, C. M., Mäbert, K., Rauen, T., & Tsokos, G. C. (2016) · Epigenomics · doi:10.2217/epi-2016-0096 · Cited by 142
miR-146a modulates autoreactive Th17 cell differentiation and regulates organ-specific autoimmunity
Li, B., Wang, X., Choi, I. Y., Wang, Y.-C., Liu, S., Pham, A. T., Moon, H., Smith, D. J., Rao, D. S., Boldin, M. P., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci94012 · Cited by 132
Cheung, K. L., Zhang, F., Jaganathan, A., Sharma, R., Zhang, Q., Konuma, T., Shen, T., Lee, J., Ren, C., Chen, C., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2016.12.022 · Cited by 143
“Th17 cell development from naïve CD4+ T cells is tightly regulated in gene transcription (Kanno et al., 2012; Medzhitov and Horng, 2009) by Th17specific orphan nuclear receptor RORγT (Ivanov et al.”
Exploiting Mucosal Immunity for Antiviral Vaccines
Iwasaki, A. (2016) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112315 · Cited by 138
Cheung, K., Lu, G., Sharma, R., Vincek, A. S., Zhang, R., Plotnikov, A. N., Zhang, F., Zhang, Q., Ju, Y., Hu, Y., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1615601114 · Cited by 132
Krishnamoorthy, V., Kannanganat, S., Maienschein‐Cline, M., Cook, S. L., Chen, J., Bahroos, N., Sievert, E. P., Corse, E., Chong, A. S., & Sciammas, R. (2017) · Immunity · doi:10.1016/j.immuni.2017.09.001 · Cited by 129
“In addition, members of the cytokine-activated STAT family of transcription factors play complex roles in Th cell formation (Kanno et al., 2012).”
InfluentialT follicular helper cell diversity and plasticity
Cannons, J. L., Lu, K. T., & Schwartzberg, P. L. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.01.001 · Cited by 130
“Such post-translational modifications relax or condense the chromatin structure to activate or repress gene transcription [94, 95] and these epigenetic changes can reflect both the transcriptional patterns as well as the transcriptional potential of DNA.”
BackgroundUnconventional post-translational modifications in immunological signaling
Mowen, K. A., & David, M. (2014) · Nature Immunology · doi:10.1038/ni.2873 · Cited by 124
Functional immune cell–astrocyte interactions
Sanmarco, L. M., Polonio, C. M., Wheeler, M. A., & Quintana, F. J. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20202715 · Cited by 134
Complex interactions of transcription factors in mediating cytokine biology in T cells
Li, P., Spolski, R. J., Liao, W., & Leonard, W. J. (2014) · Immunological Reviews · doi:10.1111/imr.12199 · Cited by 124
Bhaumik, S., & Basu, R. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00254 · Cited by 119
Autophagy and Mammalian Viruses
Paul, P., & Münz, C. (2016) · Advances in virus research · doi:10.1016/bs.aivir.2016.02.002 · Cited by 119
“Two main T cell lineages exist, namely cytotoxic CD8+ T cells and helper CD4+ T cells, which orchestrate adaptive immune responses (Kanno et al., 2012).”
BackgroundLiu, Z., Cao, W., Xu, L., Chen, X., Zhan, Y., Yang, Q., Liu, S., Chen, P., Jiang, Y., Sun, X., et al. (2015) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjv022 · Cited by 121
“Epigenetic regulators of histone modification have been shown to integrate with transcription factors to regulate the program of T cell differentiation by controlling chromatin structure and DNA accessibility (Wei et al., 2009; Zhu et al., 2010; Kanno et al., 2012).”
The polycomb repressive complex 2 governs life and death of peripheral T cells
Zhang, Y., Kinkel, S., Maksimovic, J., Bandala‐Sanchez, E., Tanzer, M. C., Naselli, G., Zhang, J., Zhan, Y., Lew, A. M., Silke, J., et al. (2014) · Blood · doi:10.1182/blood-2013-12-544106 · Cited by 118
Redefining the IBDs using genome-scale molecular phenotyping
Furey, T. S., Sethupathy, P., & Sheikh, S. Z. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0118-x · Cited by 120
Adoue, V., Binet, B., Malbec, A., Fourquet, J., Romagnoli, P., van Meerwijk, J. P. M., Amigorena, S., & Joffre, O. P. (2019) · Immunity · doi:10.1016/j.immuni.2019.01.003 · Cited by 119
Transcriptional and epigenetic regulation of T‐helper lineage specification
Tripathi, S. K., & Lahesmaa, R. (2014) · Immunological Reviews · doi:10.1111/imr.12204 · Cited by 118
“In addition, we point out the role of various epigenetic mechanisms in controlling the expression of lineage-specific genes important for determining the fate of specific cell lineage (4, 7, 10, 11).”
BackgroundInfluentialPathogenic CD4+ T cells in patients with asthma
Muehling, L. M., Lawrence, M. G., & Woodfolk, J. A. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.02.025 · Cited by 113
The Single-Cell Phenotypic Identity of Human CD8+ and CD4+ T Cells
Brummelman, J., Pilipow, K., & Lugli, E. (2018) · International review of cytology · doi:10.1016/bs.ircmb.2018.05.007 · Cited by 113
Helper T‐cell identity and evolution of differential transcriptomes and epigenomes
Vahedi, G., Poholek, A. C., Hand, T. W., Laurence, A. D. J., Kanno, Y., O’Shea, J. J., & Hirahara, K. (2013) · Immunological Reviews · doi:10.1111/imr.12037 · Cited by 112
“These observations suggest that STATs act on genes via multiple mechanisms, presumably in concert with other transcription factors (174).”
BackgroundSelf-citationMatthias, J., Maul, J., Noster, R., Meinl, H., Chao, Y.-Y., Gerstenberg, H., Jeschke, F., Gasparoni, G., Welle, A., Walter, J., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aau0683 · Cited by 105
van Panhuys, N. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00006 · Cited by 114
“As these transcription factors are tightly regulated by both kinases and phosphatases, differentiation requires an interplay between the cycling of transcription factors between inactive/cytosolic and active/nuclear states, such that threshold concentrations of localized activated factors may be required in order to m…”
BackgroundMethyltransferase G9A regulates T cell differentiation during murine intestinal inflammation
Antignano, F., Burrows, K., Hughes, M. R., Han, J. M., Kron, K. J., Penrod, N. M., Oudhoff, M. J., Wang, S. K. H., Min, P. H., Gold, M. J., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci69592 · Cited by 104
“org Volume 124 Number 5 May 2014 genetic mechanisms (20).”
Gray, S. M., Kaech, S. M., & Staron, M. M. (2014) · Immunological Reviews · doi:10.1111/imr.12205 · Cited by 105
Nestor, C. E., Barrenäs, F., Wang, H., Lentini, A., Zhang, H., Bruhn, S., Jörnsten, R., Langston, M. A., Rogers, G., Gustafsson, M., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004059 · Cited by 92
“subtypes [7].”
Harusato, A., Abo, H., Ngo, V. L., Yi, S. W., Mitsutake, K., Osuka, S., Kohlmeier, J. E., Li, J., Gewirtz, A. T., Nusrat, A., et al. (2017) · Mucosal Immunology · doi:10.1038/mi.2017.21 · Cited by 104
“Effector Th cells (Teff), on the other hand, can be grouped into several general categories (Th1, Th2, Th9, Th17, Th22, and TFH) based on dominant signature cytokines produced and associated master transcription factors expressed.(4) Interestingly, specific cytokines and factors are involved in dictating differentiati…”
BackgroundHedrich, C. M. (2017) · Current Rheumatology Reports · doi:10.1007/s11926-017-0685-1 · Cited by 99
T cells in asthma: Influences of genetics, environment, and T-cell plasticity
Lloyd, C. M., & Saglani, S. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.02.016 · Cited by 95
Zhang, L., Fang, K., Liu, Z., Bai, J., Liu, J., Yan, S., Xu, Z., Lou, F., Wang, H., Zhu, H., et al. (2015) · Nature Communications · doi:10.1038/ncomms8639 · Cited by 92
Epigenetic regulation of T‐helper cell differentiation, memory, and plasticity in allergic asthma
Tumes, D. J., Papadopoulos, M., Endo, Y., Onodera, A., Hirahara, K., & Nakayama, T. (2017) · Immunological Reviews · doi:10.1111/imr.12560 · Cited by 92
Self-citationRole of micro RNA s and long‐non‐coding RNA s in CD 4+ T‐cell differentiation
Pagani, M., Rossetti, G., Panzeri, I., de Candia, P., Bonnal, R. J. P., Rossi, R. L., Geginat, J., & Abrignani, S. (2013) · Immunological Reviews · doi:10.1111/imr.12055 · Cited by 89
“Interestingly, T lymphocytes maintain these bivalent domains even after lineage commitments are established (6), so suggesting that many differentiation events driven by instructive clues can be further modulated by tissue-specific signals that result in an environment dependent plasticity of CD4 T cells.”
BackgroundTranscriptional and epigenetic networks of helper T and innate lymphoid cells
Shih, H., Sciumè, G., Poholek, A. C., Vahedi, G., Hirahara, K., Villarino, A. V., Bonelli, M. M., Bosselut, R., Kanno, Y., Muljo, S. A., et al. (2014) · Immunological Reviews · doi:10.1111/imr.12208 · Cited by 91
Self-citationClinical reviews in allergy and immunology
Leung, D. Y. M., Ledford, D. K., Wechsler, M. E., Fulkerson, P. C., Bochner, B. S., Gauvreau, G. M., Gleich, G. J., Henkel, T., Kolbeck, R., Mathur, S. K., et al. (2012) · Cited by 87
A mitochondrial STAT3-methionine metabolism axis promotes ILC2-driven allergic lung inflammation
Fu, L., Zhao, J., Huang, J., Li, N., Dong, X. Z., He, Y., Wang, W., Wang, Y., Qiu, J., & Guo, X. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.12.783 · Cited by 83
From thymus to tissues and tumors: A review of T-cell biology
Chopp, L. B., Redmond, C., O’Shea, J. J., & Schwartz, D. M. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.10.011 · Cited by 93
Self-citationKim, K., Srikanth, S., Tan, Y., Yee, M.-K. W., Jew, M., Damoiseaux, R. D., Jung, M. E., Shimizu, S., An, D. S., Ribalet, B., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1302586 · Cited by 81
Martínez-Sánchez, M. E., Mendoza, L., Villarreal, C., & Alvarez-Buylla, E. R. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004324 · Cited by 77
“The TSRN model may lack components, interactions or epigenetic mechanisms of regulation that are important to enabling such direct transitions [33].”
Identity crisis of Th17 cells: many forms, many functions, many questions
Sundrud, M. S., & Trivigno, C. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.10.021 · Cited by 77
“, H3K27tri-me, 3K9tri-me) are removed (reviewed in [61,62]).”
Nagata, D. D. A., Ting, H.-A., Cavassani, K. A., Schaller, M. A., Mukherjee, S., Ptaschinski, C., Kunkel, S. L., & Lukacs, N. W. (2015) · Mucosal Immunology · doi:10.1038/mi.2015.4 · Cited by 78
New roles for cyclin-dependent kinases in T cell biology: linking cell division and differentiation
Wells, A. D., & Morawski, P. A. (2014) · Nature reviews. Immunology · doi:10.1038/nri3625 · Cited by 78
Meng, X., Liu, J., Liu, S., Chen, K., Lin, H., Jiang, M., Xu, X., Xue, Y., Liu, W., Gu, Y. H., et al. (2017) · Nature Communications · doi:10.1038/ncomms15818 · Cited by 73
Effector γδ T Cell Differentiation Relies on Master but Not Auxiliary Th Cell Transcription Factors
Barros‐Martins, J., Schmolka, N., Fontinha, D., de Miranda, M. P., Simas, J. P., Brok, I. C., Ferreira, C., Veldhoen, M., Silva‐Santos, B., & Serre, K. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1501921 · Cited by 76
“target loci, including those of the signature cytokines (23).”
BackgroundCook, P. C., Owen, H., Deaton, A. M., Borger, J. G., Brown, S. L., Clouaire, T., Jones, G., Jackson-Jones, L. H., Lundie, R. J., Marley, A. K., et al. (2015) · Nature Communications · doi:10.1038/ncomms7920 · Cited by 75
“In recent years, it has become clear that ‘epigenetic’ mechanisms, which alter gene expression without changing underlying DNA sequence, play an important role in regulating multiple aspects of T cell differentiation and function 22,23 .”
Zimmermann, M. T., Oberg, A. L., Grill, D. E., Ovsyannikova, I. G., Haralambieva, I. H., Kennedy, R. B., & Poland, G. A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0152034 · Cited by 71
Hedrich, C. M., Crispín, J. C., & Tsokos, G. C. (2014) · Autoimmunity · doi:10.3109/08916934.2013.801462 · Cited by 74
“Because T helper lymphocyte subset determination and signature cytokine expression are largely controlled by epigenetic mechanisms [54], it appears likely that estrogens affect chromatin composition of lineage-defining genes in T”
BackgroundDefining CD4 T Cell Memory by the Epigenetic Landscape of CpG DNA Methylation
Komori, H. K., Hart, T., LaMere, S. A., Chew, P. V., & Salomon, D. R. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1401162 · Cited by 74
“The advent of complementary high-throughput technologies [e.g., ChIPseq, MethylSeq (77)] has allowed investigators to begin to address such sophisticated biological questions.”
Lu, M. S., Taylor, B. V., & Körner, H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00477 · Cited by 73
“Therefore, a genome-wide enhancer landscape of active enhancers was identified using the ChIP-seq method (135, 136).”
MethodThe 4E-BP–eIF4E axis promotes rapamycin-sensitive growth and proliferation in lymphocytes
So, L., Lee, J., Palafox, M., Mallya, S., Woxland, C. G., Arguello, M., Truitt, M., Sonenberg, N., Ruggero, D., & Fruman, D. A. (2016) · Science Signaling · doi:10.1126/scisignal.aad8463 · Cited by 72
Epigenetics of Inflammation, Maternal Infection, and Nutrition1–3
Claycombe, K., Brissette, C. A., & Ghribi, O. (2015) · Journal of Nutrition · doi:10.3945/jn.114.194639 · Cited by 68
“Epigenetic regulation, including histone modification and DNA methylation, is important for T cell differentiation, including T helper (Th) 1 and Th2 subsets, as well as for regulatory T cells and the Th17 lineage (16, 17).”
BackgroundSchistosomiasis Induces Persistent DNA Methylation and Tuberculosis-Specific Immune Changes
DiNardo, A. R., Nishiguchi, T., Mace, E. M., Rajapakshe, K., Mtetwa, G., Kay, A. W., Maphalala, G. P., Secor, W. E., Mejía, R., Orange, J. S., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800101 · Cited by 66
Role of miRNAs in CD4 T cell plasticity during inflammation and tolerance
Sethi, A., Kulkarni, N., Sonar, S. A., & Lal, G. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00008 · Cited by 70
“REVIEW ARTICLE published: 31 January 2013 doi: 10.3389/fgene.2013.00008 Role of miRNAs in CD4 T cell plasticity during inflammation and tolerance”
BackgroundInfluentialCutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt RORγt+ and Follicular Phenotypes
Wheaton, J. D., Yeh, C., & Ciofani, M. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1701134 · Cited by 70
“lymphoma (Bcl)-6 (T follicular helper [Tfh]) (2).”
Epigenetic Control of Cytokine Gene Expression
Falvo, J. V., Jasenosky, L. D., Kruidenier, L., & Goldfeld, A. E. (2013) · Advances in immunology · doi:10.1016/b978-0-12-407708-9.00002-9 · Cited by 69
“and/or mediate higher-order chromatin structure (Amsen et al., 2009; Balasubramani, Mukasa, Hatton, & Weaver, 2010; Hatton et al., 2006; Kanno et al., 2012; Lee, Avni, Chen, & Rao, 2004; Shnyreva et al., 2004; Wilson et al., 2009).”
BackgroundInfluentialNew candidates for CD4 T cell pathogenicity in experimental neuroinflammation and multiple sclerosis
Hoppmann, N., Graetz, C., Paterka, M., Poisa-Beiro, L., Larochelle, C., Hasan, M., Lill, C. M., Zipp, F., & Siffrin, V. (2015) · Brain · doi:10.1093/brain/awu408 · Cited by 66
“In this respect, Th17 cells showed strong plasticity as they can be reprogrammed into different lineages in various differentiation states (Zhu and Paul, 2010; Kanno et al., 2012).”
BackgroundHelper T Cell Plasticity: Impact of Extrinsic and Intrinsic Signals on Transcriptomes and Epigenomes
Bonelli, M. M., Shih, H., Hirahara, K., Singelton, K., Laurence, A. D. J., Poholek, A. C., Hand, T., Mikami, Y., Vahedi, G., Kanno, Y., et al. (2014) · Current topics in microbiology and immunology · doi:10.1007/82_2014_371 · Cited by 66
“, which all contribute to define the overall structure of chromatin (Rivera and Ren 2013; Kanno et al. 2012) (Fig.”
InfluentialSelf-citation
Metadata
- Authors
- Kanno, Y., Vahedi, G., Hirahara, K., Singleton, K., & O'Shea, J. J.
- Affiliations
- National Institutes of Health (US)
- Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892;
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 2012-04-23
- Volume
- 30
- Issue
- 1
- Pages
- 707-731
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- PMC
- PMC3314163
- OpenAlex
- W2095649879
- Cited by
- 342
- References
- 163
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 12 · 2023: 10 · 2022: 16 · 2021: 19 · 2020: 13 · 2019: 21 · 2018: 22 · 2017: 33 · 2016: 34 · 2015: 49 · 2014: 45 · 2013: 40 · 2012: 9
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99‐AA999999, Z99 AR999999, Z99 DA999999)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- T helper cell differentiation, transcription factors, chromatin modification, epigenetics, STAT signaling, T cell receptor signaling, cytokine signaling, T cell transcriptome, T cell plasticity, signal transduction
- MeSH terms
- Animals, Autoimmune Diseases, Cell Differentiation, Gene Expression Regulation, T-Lymphocytes, Helper-Inducer, Humans, Transcription Factors, Transcription, Genetic, Cell Lineage, RNA, Untranslated, Epigenesis, Genetic, Regulatory Elements, Transcriptional, Epigenomics
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