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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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“Activating enhancers in immune cells typically involves specific histone modifications, notably histone H3 lysine 27 acetylation (H3K27ac) and lysine 4 monomethylation (H3K4me1) (52).”
CD4+ T Cells Mediate Aspergillosis Vaccine Protection
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Role of Th1 and Th2 in autoimmunity
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How epigenetic imprinting contributes to stabilizing the Th2 phenotype
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Engineered probiotics limit CNS autoimmunity by stabilizing HIF-1α in dendritic cellsPreprint
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Transcriptional co-regulator OCA-B/Pou2af1 restricts Th2 differentiation
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“As a given Th lineage is established, lineage-inappropriate genes are silenced such that other Th lineages are suppressed (5 – 8).”
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Epigenetic Control of Immune T Cell Memory
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“These factors orchestrate the activation of gene subsets related to a particular committed T cells while shutting down the transcription of all the other genes (Kanno et al., 2012).”
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Cancer Immunity and Immune Evasion Mechanisms
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Defining Barriers that Impede Choices
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Epigenetics and the Regulation of Inflammation
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Overview of Hematopoietic Cell Transplantation Immunology
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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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