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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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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
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Items 301–346 of 346
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Self-citationKommer, C., Zhang, Q., Hegazy, A. N., Löhning, M., & Höfer, T. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.23.517729 · Cited by 1
“…autoactivation loops stabilize both GATA-3 and T-bet expression, and there are numerous inhibitory interactions between Th1-and Th2-inducing molecular pathways (Ouyang et al., 2000; Mullen et al., 2001; Afkarian et al., 2002; Peine et al., 2013; Kanno et al., 2012; L¨ohning et al., 2002).”
BackgroundIn Vitro Models of Alloreactivity
Su, C. A., Valujskikh, A., Baldwin, W. M., & Fairchild, R. L. (2014) · Wiley eBooks · doi:10.1002/9781118873434.ch13
T‐Zellplastizität bei entzündlichen Hauterkrankungen – die Guten, die Schlechten und die Chamäleons
Gatzka, M., & Scharffetter‐Kochanek, K. (2015) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1111/ddg.120_12677
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Maltzman, J. S., Thomson, A. W., & Rothstein, D. M. (2015) · Transplant Immunology · doi:10.1002/9781119072997.ch6
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Voice, M. A. (2015) · University of Birmingham Institutional Research Archive (University of Birmingham)
The role of regulatory T and B cells in host responses to Chlamydia genital tract infection
Moore-Connors, J. (2016) · DalSpace (Dalhousie University)
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Awe, O. (2015) · IUScholarWorks (Indiana University) · doi:10.7912/c2/1724
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Amorim, A. (2014) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/h70p-6p39
Gwack, Y., Ribalet, B., Jew, M., Damoiseaux, R. D., Jung, M. E., Kim, K., & Srikanth, S. (2014)
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Amorim, D. O. R. (2014)
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Gros, G. S. L., & Kyle, R. L. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-374279-7.08003-6
Immunity and Disease Mechanisms of Jak/STAT Signaling in
O’Shea, J. J., Villarino, A. V., Kanno, Y., & Ferdinand, J. R. (2015)
Self-citationDoerner, S. K. (2013) · OhioLink ETD Center (Ohio Library and Information Network)
Nichiporuk Stumpf, E., Yeung, M. Y., Grimm, M. R., Grimmig, T., Stern, P. L., Moench, R., Lebedeva, T., Pál, S., Tripathi, S. C., Bonventre, J. V., et al. (2017) · Journal of Clinical & Cellular Immunology · doi:10.4172/2155-9899.1000511
MicroRNA and T Helper Cell-Mediated Immune Responses
Garo, L. P., Beynon, V., & Murugaiyan, G. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809912-4.00004-0
Locus specific DNA methylation in human immunological responses
Bergman, E. A. (2018) · Figshare
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Massoud, A. H., & Chatila, T. A. (2019) · Selçuk Tıp Dergisi · doi:10.30733/std.2019.01147
“Thus, the differentiation of the effector TH1, TH2 or TH17 subsets requires the expression of the TH cell lineage committing transcription factors T-bet, GATA-3 and ROR-γt, respectively, whereas Treg cells require FOXP3 expression (30).”
BackgroundEpigenetic biomarkers of asthma and allergic disorders
Akhtari, M., & Mahmoudi, M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814259-2.00007-8 · Cited by 1
Molecular Regulation of SATB1 in Regulatory T-cells
Thabet, Y. (2013) · bonndoc (University of Bonn)
Liu, A. H., Johnston, R. B., & Fenton, M. J. (2014) · Elsevier eBooks · doi:10.1016/b978-0-323-08593-9.00002-4
Guersetti, E. (2019) · Open Collections · doi:10.14288/1.0375853
Alvarez-Buylla, E. R., Martínez‐García, J. C., Dávila-Velderrain, J., Domínguez‐Hüttinger, E., & Martínez-Sánchez, M. E. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-89354-9_3
Maizels, R. M. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733222522.793555267
Monticelli, S. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718509023.793551839
Lymphocytes: Antigen‐Induced Gene Activation
Suárez‐Fueyo, A., Madrenas, J., & Criado, G. (2013) · Wiley eBooks · doi:10.1002/9780470015902.a0001191.pub3
Михайловна, М. А., Евгеньевна, М. Н., & Pashenkov, M. V. (2022) · Immunologiya · doi:10.33029/0206-4952-2022-43-6-722-736
Zouei, N., Dalimi, A., Pirestani, M., & Ghaffarifar, F. (2023) · Microbial Pathogenesis · doi:10.1016/j.micpath.2023.106340
Synergistic roles of NFATc1 and c-Jun in immunomodulation
Cao, B., & Wei, R. (2025) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2025.102137
The Role of Notch Signaling in T Cell-mediated Immune Disorders.
Sandy, A. R. (2013) · Deep Blue (University of Michigan)
Yu, L., Wei, Y., Lu, T., Li, Z., Lai, S., Yan, Y., Chen, C., & Wen, W. (2024) · Figshare · doi:10.6084/m9.figshare.26647515
Yu, L., Wei, Y., Lu, T., Li, Z., Lai, S., Yan, Y., Chen, C., & Wen, W. (2024) · Figshare · doi:10.6084/m9.figshare.26647506
Yu, L., Wei, Y., Lu, T., Li, Z., Lai, S., Yan, Y., Chen, C., & Wen, W. (2024) · Figshare · doi:10.6084/m9.figshare.26647503
Yu, L., Wei, Y., Lu, T., Li, Z., Lai, S., Yan, Y., Chen, C., & Wen, W. (2024) · Figshare · doi:10.6084/m9.figshare.26647509
Yu, L., Wei, Y., Lu, T., Li, Z., Lai, S., Yan, Y., Chen, C., & Wen, W. (2024) · Figshare · doi:10.6084/m9.figshare.26647518
Yu, L., Wei, Y., Lu, T., Li, Z., Lai, S., Yan, Y., Chen, C., & Wen, W. (2024) · Figshare · doi:10.6084/m9.figshare.26647512
Contrôle épigénétique de la biologie des lymphocytes T CD4
Malbec, A. (2018) · theses.fr (ABES) · doi:10.70675/6286d187zb91fz4014z9075z77e8f3c56b09
Facteurs génétiques et post-génétiques associés au développement de la sclérose en plaques
Axisa, P. (2017) · theses.fr (ABES) · doi:10.70675/bd87267ez6461z4759z8173z6f34bba4e52f
T-helper subpopulations and their biological effects
Витальевич, М. А., Gumilevsky, B. Y., Gumilevskaya, O. P., Zhestkov, A. V., Башкина, О. А., Денисовна, В. Л., & Starova, J. A. (2026) · ASTRAKHAN MEDICAL JOURNAL · doi:10.17021/1992-6499-2026-2-35-47
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InfluentialChen, Y., Yu, L., Yang, R., Chen, P., Zeng, W., Li, Z., Wang, Y., 许勇钢, & Yang, X. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08835-2
“It promotes the differentiation and memory formation of CD8 ⁺ cytotoxic T cells (Tc) [12–14], whilst stabilising the lineage identity of regulatory T cells (Treg) and CD4 ⁺ helper T cell (Th) subsets [15–17].”
Chudakov, D. M. (2026) · Immunological Reviews · doi:10.1111/imr.70172
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Lv, M., Ding, J., Long, H., Chai, Q., Xu, L., Jin, C., Liang, W., Zhang, L., Zhang, B., Lv, Z., et al. (2026) · Science Advances · doi:10.1126/sciadv.aee8251
“They dynamically regulate transcriptional programs that control lineage commitment, long-term memory formation, and the development of T cell exhaustion ( 6 – 11 ).”
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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