Molecular Mechanisms of T Helper Cell Differentiation and Functional Specialization
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Th cells, which orchestrate immune responses to various pathogens, differentiate from naïve CD4 T cells into several subsets that stimulate and regulate immune responses against various types of pathogens, as well as a variety of immune-related diseases. Decades of research have revealed that the fate decision processes are controlled by cytokines, cytokine receptor signaling, and master transcription factors that drive the differentiation programs. Since the Th1 and Th2 paradigm was proposed, many subsets have been added to the list. In this review, I will summarize these events, including the fate decision processes, subset functions, transcriptional regulation, metabolic regulation, and plasticity and heterogeneity. I will also introduce current topics of interest.
Abstract
Th cells, which orchestrate immune responses to various pathogens, differentiate from naïve CD4 T cells into several subsets that stimulate and regulate immune responses against various types of pathogens, as well as a variety of immune-related diseases. Decades of research have revealed that the fate decision processes are controlled by cytokines, cytokine receptor signaling, and master transcription factors that drive the differentiation programs. Since the Th1 and Th2 paradigm was proposed, many subsets have been added to the list. In this review, I will summarize these events, including the fate decision processes, subset functions, transcriptional regulation, metabolic regulation, and plasticity and heterogeneity. I will also introduce current topics of interest.
참고문헌 (90)
- Saravia J, "Helper T cell differentiation", Cell Mol Immunol, 16, pp.634~643 (2019)
- O’Shea JJ, "Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells", Science, 327, pp.1098~1102 (2010)
- Murphy KM, "Signaling and transcription in T helper development", Annu Rev Immunol, 18, pp.451~494 (2000)
- Zhu J, "Differentiation of effector CD4 T cell populations(*)", Annu Rev Immunol, 28, pp.445~489 (2010)
- Mosmann TR, "Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins", J Immunol, 136, pp.2348~2357 (1986)
- Bettelli E, "IL-12-and IL-23-induced T helper cell subsets : birds of the same feather flock together", J Exp Med, 201, pp.169~171 (2005)
- Harrington LE, "Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages", Nat Immunol, 6, pp.1123~1132 (2005)
- Park H, "A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17", Nat Immunol, 6, pp.1133~1141 (2005)
- Patel DD, "Th17 cell pathway in human immunity : lessons from genetics and therapeutic interventions", Immunity, 43, pp.1040~1051 (2015)
- Ouyang W, "The biological functions of T helper 17 cell effector cytokines in inflammation", Immunity, 28, pp.454~467 (2008)
- Chtanova T, "T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1", Th2 effector cells that provide help for B cells, 2004, pp.173, 68~78
- Nurieva RI, "Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages", Immunity, 29, pp.138~149 (2008)
- Kim CH, "Unique gene expression program of human germinal center T helper cells", Blood, 104, pp.1952~1960 (2004)
- Sakaguchi S, "Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains(CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases", J Immunol, 155, pp.1151~1164 (1995)
- Veldhoen M, "Transforming growth factor-beta ‘reprograms’ the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset", Nat Immunol, 9, pp.1341~1346 (2008)
- Dardalhon V, "IL-4 inhibits TGF-β-induced Foxp3+ T cells and, together with TGF-β, generates IL-9+ IL-10+ Foxp3-effector T cells", Nat Immunol, 9, pp.1347~1355 (2008)
- Murray PJ, "Protective and pathogenic functions of macrophage subsets", Nat Rev Immunol, 11, pp.723~737 (2011)
- Maizels RM, "Regulation of pathogenesis and immunity in helminth infections", J Exp Med, 206, pp.2059~2066 (2009)
- Shulman Z, "Dynamic signaling by T follicular helper cells during germinal center B cell selection", Science, 345, pp.1058~1062 (2014)
- Kitagawa Y, "Molecular control of regulatory T cell development and function", Curr Opin Immunol, 49, pp.64~70 (2017)
- Huang CT, "Role of LAG-3 in regulatory T cells", Immunity, 21, pp.503~513 (2004)
- Paust S, "Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease", Proc Natl Acad Sci U S A, 101, pp.10398~10403 (2004)
- Deaglio S, "Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression", J Exp Med, 204, pp.1257~1265 (2007)
- Djuretic IM, "Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells", Nat Immunol, 8, pp.145~153 (2007)
- Szabo SJ, "Regulation of the interleukin(IL)-12R beta 2 subunit expression in developing T helper 1(Th1)and Th2 cells", J Exp Med, 185, pp.817~824 (1997)
- Johnston RJ, "Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation", Science, 325, pp.1006~1010 (2009)
- Nurieva RI, "Bcl6 mediates the development of T follicular helper cells", Science, 325, pp.1001~1005 (2009)
- 이지범, "Immune Checkpoint Inhibitors in 10 Years: Contribution of Basic Research and Clinical Application in Cancer Immunotherapy", Immune Network, 22(1), pp.1~22 (2022), 대한면역학회[DOI]
- 정승민, "Targeted Immunotherapy for Autoimmune Disease", Immune Network, 22(1), pp.1~23 (2022), 대한면역학회[DOI]
- Vahedi G, "STATs shape the active enhancer landscape of T cell populations", Cell, 151, pp.981~993 (2012)
- Samstein RM, "Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification", Cell, 151, pp.153~166 (2012)
- Chalmin F, "Transcriptional programs underlying Cd4 T cell differentiation and functions", Int Rev Cell Mol Biol, 341, pp.1~61 (2018)
- Christie D, "Transcriptional regulatory networks for CD4 T cell differentiation", Curr Top Microbiol Immunol, 381, pp.125~172 (2014)
- Ciofani M, "A validated regulatory network for Th17 cell specification", Cell, 151, pp.289~303 (2012)
- Yosef N, "Dynamic regulatory network controlling TH17 cell differentiation", Nature, 496, pp.461~468 (2013)
- Fu W, "A multiply redundant genetic switch ‘locks in’ the transcriptional signature of regulatory T cells", Nat Immunol, 13, pp.972~980 (2012)
- Wilson CB, "Epigenetic control of T-helper-cell differentiation", Nat Rev Immunol, 9, pp.91~105 (2009)
- Lee GR, "T helper cell differentiation : regulation by cis elements and epigenetics", Immunity, 24, pp.369~379 (2006)
- Wei G, "Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells", Immunity, 30, pp.155~167 (2009)
- Levings PP, "The human β-globin locus control region", Eur J Biochem, 269, pp.1589~1599 (2002)
- Lee GR, "Regulation of the Th2 cytokine locus by a locus control region", Immunity, 19, pp.145~153 (2003)
- Koh BH, "Th2 LCR is essential for regulation of Th2 cytokine genes and for pathogenesis of allergic asthma", Proc Natl Acad Sci U S A, 107, pp.10614~10619 (2010)
- Hwang SS, "Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation", Proc Natl Acad Sci U S A, 110, pp.276~281 (2013)
- Hwang SS, "RHS6 coordinately regulates the Th2 cytokine genes by recruiting GATA3, SATB1, and IRF4", Allergy, 72, pp.772~782 (2017)
- Lee GR, "Hypersensitive site 7 of the TH2 locus control region is essential for expressing TH2 cytokine genes and for long-range intrachromosomal interactions", Nat Immunol, 6, pp.42~48 (2005)
- Williams A, "Hypersensitive site 6 of the Th2 locus control region is essential for Th2 cytokine expression", Proc Natl Acad Sci U S A, 110, pp.6955~6960 (2013)
- Spilianakis CG, "Long-range intrachromosomal interactions in the T helper type 2 cytokine locus", Nat Immunol, 5, pp.1017~1027 (2004)
- Spilianakis CG, "Interchromosomal associations between alternatively expressed loci", Nature, 435, pp.637~645 (2005)
- Kim LK, "Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells", Mol Cell, 54, pp.56~66 (2014)
- Hadjur S, "Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus", Nature, 460, pp.410~413 (2009)
- Sekimata M, "CCCTC-binding factor and the transcription factor T-bet orchestrate T helper 1 cell-specific structure and function at the interferon-gamma locus", Immunity, 31, pp.551~564 (2009)
- Murphy E, "Reversibility of T helper 1 and 2 populations is lost after long-term stimulation", J Exp Med, 183, pp.901~913 (1996)
- Grogan JL, "Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets", Immunity, 14, pp.205~215 (2001)
- Ballesteros-Tato A, "T follicular helper cell plasticity shapes pathogenic T helper 2 cell-mediated immunity to inhaled house dust mite", Immunity, 44, pp.259~273 (2016)
- Zhou L, "Plasticity of CD4+ T cell lineage differentiation", Immunity, 30, pp.646~655 (2009)
- Hirota K, "Fate mapping of IL-17-producing T cells in inflammatory responses", Nat Immunol, 12, pp.255~263 (2011)
- Bending D, "Highly purified Th17 cells from BDC2. 5NOD mice convert into Th1-like cells in NOD", SCID recipient mice, 2009, pp.119, 565~572
- Muranski P, "Th17 cells are long lived and retain a stem cell-like molecular signature", Immunity, 35, pp.972~985 (2011)
- Ivanov II, "The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells", Cell, 126, pp.1121~1133 (2006)
- Okada S, "Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations", Science, 349, pp.606~613 (2015)
- Koch MA, "The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation", Nat Immunol, 10, pp.595~602 (2009)
- Wan YY, "Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression", Nature, 445, pp.766~770 (2007)
- Zheng Y, "Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses", Nature, 458, pp.351~356 (2009)
- Chaudhry A, "CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner", Science, 326, pp.986~991 (2009)
- Roy S, "Metabolic checkpoints in differentiation of helper T cells in tissue inflammation", Front Immunol, 9, pp.3036~ (2019)
- Almeida L, "CD4+ T-cell differentiation and function : unifying glycolysis, fatty acid oxidation, polyamines NAD mitochondria", J Allergy Clin Immunol, 148, pp.16~32 (2021)
- Yang W, "CD4+ T cell metabolism, gut microbiota, and autoimmune diseases: implication in precision medicine of autoimmune diseases", Precis Clin Med, 5 (2022)
- Xu K, "Glycolytic ATP fuels phosphoinositide 3-kinase signaling to support effector T helper 17 cell responses", Immunity, 54, pp.976~987 (2021)
- Shi LZ, "HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells", J Exp Med, 208, pp.1367~1376 (2011)
- Michalek RD, "Cutting edge : distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets", J Immunol, 186, pp.3299~3303 (2011)
- Wang R, "The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation", Immunity, 35, pp.871~882 (2011)
- Preston GC, "Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes", EMBO J, 34, pp.2008~2024 (2015)
- Man K, "Synchronizing transcriptional control of T cell metabolism and function", Nat Rev Immunol, 15, pp.574~584 (2015)
- McNamee EN, "Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function", Immunol Res, 55, pp.58~70 (2013)
- Dang EV, "Control of TH17", Treg balance by hypoxia-inducible factor 1, 2011, pp.146, 772~784
- Doedens AL, "Hypoxia-inducible factors enhance the effector responses of CD8+ T cells to persistent antigen", Nat Immunol, 14, pp.1173~1182 (2013)
- Phan AT, "Constitutive glycolytic metabolism supports CD8+ T cell effector memory differentiation during viral infection", Immunity, 45, pp.1024~1037 (2016)
- Clever D, "Oxygen sensing by T cells establishes an immunologically tolerant metastatic niche", Cell, 166, pp.1117~1131 (2016)
- Delgoffe GM, "The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment", Immunity, 30, pp.832~844 (2009)
- Delgoffe GM, "The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2", Nat Immunol, 12, pp.295~303 (2011)
- Lee K, "Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways", Immunity, 32, pp.743~753 (2010)
- Shrestha S, "Treg cells require the phosphatase PTEN to restrain TH1 and TFH cell responses", Nat Immunol, 16, pp.178~187 (2015)
- Huynh A, "Control of PI(3)kinase in Treg cells maintains homeostasis and lineage stability", Nat Immunol, 16, pp.188~196 (2015)
- Hardie DG, "AMP-activated protein kinase : an energy sensor that regulates all aspects of cell function", Genes Dev, 25, pp.1895~1908 (2011)
- Meares GP, "AMP-activated protein kinase restricts IFN-γ signaling", J Immunol, 190, pp.372~380 (2013)
- Gaublomme JT, "Single-cell genomics unveils critical regulators of Th17 cell pathogenicity", Cell, 163, pp.1400~1412 (2015)
- Karmaus PW, "Metabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity", Nature, 565, pp.101~105 (2019)
- Tortola L, "High-dimensional T helper cell profiling reveals a broad diversity of stably committed effector states and uncovers interlineage relationships", Immunity, 53, pp.597~613 (2020)
- Kiner E, "Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes", Nat Immunol, 22, pp.216~228 (2021)
- Lönnberg T, "Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1", Tfh fate bifurcation in malaria, 2017, pp.2, ~
