The Balance of Th17 Versus Treg Cells in Autoimmunity

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2018 Mar 8

PMID 29510522

Citations 353

Authors

Gap Ryol Lee

Affiliations

Soon will be listed here.

Abstract

T helper type 17 (Th17) cells and pTreg cells, which share a common precursor cell (the naïve CD4 T cell), require a common tumor growth factor (TGF)-β signal for initial differentiation. However, terminally differentiated cells fulfill opposite functions: Th17 cells cause autoimmunity and inflammation, whereas Treg cells inhibit these phenomena and maintain immune homeostasis. Thus, unraveling the mechanisms that affect the Th17/Treg cell balance is critical if we are to better understand autoimmunity and tolerance. Recent studies have identified many factors that influence this balance; these factors range from signaling pathways triggered by T cell receptors, costimulatory receptors, and cytokines, to various metabolic pathways and the intestinal microbiota. This review article summarizes recent advances in our understanding of the Th17/Treg balance and its implications with respect to autoimmune disease.

Citing Articles

Umbilical mesenchymal stem cells mitigate T-cell compartments shift and Th17/Treg imbalance in acute ischemic stroke via mitochondrial transfer.

Chen S, Han C, Shi Z, Guan X, Cheng L, Wang L Stem Cell Res Ther. 2025; 16(1):134.

PMID: 40075467 PMC: 11905603. DOI: 10.1186/s13287-025-04224-6.

Impact of immune cell metabolism on membranous nephropathy and prospective therapy.

Duan X, Lv X, Wang X, Zhang Y, Hu Y, Li H Commun Biol. 2025; 8(1):405.

PMID: 40065158 PMC: 11893770. DOI: 10.1038/s42003-025-07816-3.

Leveraging the Immunomodulatory Potential of Ibrutinib for Improved Outcomes of T Cell-Mediated Therapies of B Cell Malignancies: A Narrative Review.

Miklos D, Riedell P, Bokun A, Chavez J, Schuster S Target Oncol. 2025; .

PMID: 40035913 DOI: 10.1007/s11523-025-01133-9.

Wang H, Li Y, Li H, Yan X, Jiang Z, Feng L J Orthop Translat. 2025; 51:82-93.

PMID: 39991456 PMC: 11847249. DOI: 10.1016/j.jot.2024.12.004.

New perspectives on DNA methylation modifications in ocular diseases.

Zong F, Jia D, Huang G, Pan M, Hu H, Song S Int J Ophthalmol. 2025; 18(2):340-350.

PMID: 39967986 PMC: 11754021. DOI: 10.18240/ijo.2025.02.19.

References

Vaeth M, Schliesser U, Muller G, Reissig S, Satoh K, Tuettenberg A . Dependence on nuclear factor of activated T-cells (NFAT) levels discriminates conventional T cells from Foxp3+ regulatory T cells. Proc Natl Acad Sci U S A. 2012; 109(40):16258-63. PMC: 3479579. DOI: 10.1073/pnas.1203870109. View

Kim S, Xiang W, Kwak C, Yang Y, Lin X, Ota M . GPR15-mediated homing controls immune homeostasis in the large intestine mucosa. Science. 2013; 340(6139):1456-9. PMC: 3762262. DOI: 10.1126/science.1237013. View

Zhou L, Chong M, Littman D . Plasticity of CD4+ T cell lineage differentiation. Immunity. 2009; 30(5):646-55. DOI: 10.1016/j.immuni.2009.05.001. View

MacIver N, Michalek R, Rathmell J . Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013; 31:259-83. PMC: 3606674. DOI: 10.1146/annurev-immunol-032712-095956. View

Bettelli E, Carrier Y, Gao W, Korn T, Strom T, Oukka M . Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006; 441(7090):235-8. DOI: 10.1038/nature04753. View

Hwang S, Jang S, Kim M, Kim L, Kim B, Kim H . YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity. Nat Commun. 2016; 7:10789. PMC: 4762897. DOI: 10.1038/ncomms10789. View

Dang E, Barbi J, Yang H, Jinasena D, Yu H, Zheng Y . Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 2011; 146(5):772-84. PMC: 3387678. DOI: 10.1016/j.cell.2011.07.033. View

Li S, Wu Z, Li L, Liu X . Interleukin-6 (IL-6) Receptor Antagonist Protects Against Rheumatoid Arthritis. Med Sci Monit. 2016; 22:2113-8. PMC: 4920098. DOI: 10.12659/msm.896355. View

Veldhoen M, Hocking R, Atkins C, Locksley R, Stockinger B . TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity. 2006; 24(2):179-89. DOI: 10.1016/j.immuni.2006.01.001. View

10.

Esensten J, Helou Y, Chopra G, Weiss A, Bluestone J . CD28 Costimulation: From Mechanism to Therapy. Immunity. 2016; 44(5):973-88. PMC: 4932896. DOI: 10.1016/j.immuni.2016.04.020. View

11.

Ivanov I, de Llanos Frutos R, Manel N, Yoshinaga K, Rifkin D, Sartor R . Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe. 2008; 4(4):337-49. PMC: 2597589. DOI: 10.1016/j.chom.2008.09.009. View

12.

Medoff B, Sandall B, Landry A, Nagahama K, Mizoguchi A, Luster A . Differential requirement for CARMA1 in agonist-selected T-cell development. Eur J Immunol. 2009; 39(1):78-84. PMC: 2747028. DOI: 10.1002/eji.200838734. View

13.

Gaboriau-Routhiau V, Rakotobe S, Lecuyer E, Mulder I, Lan A, Bridonneau C . The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 2009; 31(4):677-89. DOI: 10.1016/j.immuni.2009.08.020. View

14.

Chang P, Hao L, Offermanns S, Medzhitov R . The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci U S A. 2014; 111(6):2247-52. PMC: 3926023. DOI: 10.1073/pnas.1322269111. View

15.

Zhou X, Bailey-Bucktrout S, Jeker L, Penaranda C, Martinez-Llordella M, Ashby M . Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat Immunol. 2009; 10(9):1000-7. PMC: 2729804. DOI: 10.1038/ni.1774. View

16.

Siggs O, Miosge L, Yates A, Kucharska E, Sheahan D, Brdicka T . Opposing functions of the T cell receptor kinase ZAP-70 in immunity and tolerance differentially titrate in response to nucleotide substitutions. Immunity. 2007; 27(6):912-26. PMC: 3163119. DOI: 10.1016/j.immuni.2007.11.013. View

17.

Barbi J, Pardoll D, Pan F . Metabolic control of the Treg/Th17 axis. Immunol Rev. 2013; 252(1):52-77. PMC: 3576873. DOI: 10.1111/imr.12029. View

18.

Geuking M, Cahenzli J, Lawson M, Ng D, Slack E, Hapfelmeier S . Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity. 2011; 34(5):794-806. DOI: 10.1016/j.immuni.2011.03.021. View

19.

Gaffen S, Jain R, Garg A, Cua D . The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014; 14(9):585-600. PMC: 4281037. DOI: 10.1038/nri3707. View

20.

Zhu J, Paul W . Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol Rev. 2010; 238(1):247-62. PMC: 2975272. DOI: 10.1111/j.1600-065X.2010.00951.x. View