The Plasticity of Human Treg and Th17 Cells and Its Role in Autoimmunity

Overview

Journal Semin Immunol

Specialty Allergy & Immunology

Date 2013 Nov 12

PMID 24211039

Citations 209

Authors

Markus Kleinewietfeld

David A Hafler

Affiliations

Soon will be listed here.

Abstract

CD4(+) T helper cells are a central element of the adaptive immune system. They protect the organism against a wide range of pathogens and are able to initiate and control many immune reactions in combination with other cells of the adaptive and the innate immune system. Starting from a naive cell, CD4(+) T cells can differentiate into various effector cell populations with specialized function. This subset specific differentiation depends on numerous signals and the strength of stimulation. However, recent data have shown that differentiated CD4(+) T cell subpopulations display a high grade of plasticity and that their initial differentiation is not an endpoint of T cell development. In particular, FoxP3(+) regulatory T cells (Treg) and Th17 effector T cells demonstrate a high grade of plasticity, which allow a functional adaptation to various physiological situations during an immune response. However, the plasticity of Treg and Th17 cells might also be a critical factor for autoimmune disease. Here we discuss the recent developments in CD4(+) T cell plasticity with a focus on Treg and Th17 cells and its role in human autoimmune disease, in particular multiple sclerosis (MS).

Citing Articles

Association between 25(OH) vitamin D and multiple sclerosis: cohort, shared genetics, and Causality.

Yu X, Lu H, Li J, Su M, Li X, Jin Y Nutr J. 2024; 23(1):151.

PMID: 39616386 PMC: 11608472. DOI: 10.1186/s12937-024-01059-4.

Overview of mechanisms and novel therapies on rheumatoid arthritis from a cellular perspective.

Han P, Liu X, He J, Han L, Li J Front Immunol. 2024; 15:1461756.

PMID: 39376556 PMC: 11456432. DOI: 10.3389/fimmu.2024.1461756.

Proprotein convertase subtilisin/kexin type 9 deficiency in extrahepatic tissues: emerging considerations.

Lu F, Li E, Yang X Front Pharmacol. 2024; 15:1413123.

PMID: 39139638 PMC: 11319175. DOI: 10.3389/fphar.2024.1413123.

Blocking the IL-4/IL-13 Axis versus the JAK/STAT Pathway in Atopic Dermatitis: How Can We Choose?.

Calabrese L, DOnghia M, Lazzeri L, Rubegni G, Cinotti E J Pers Med. 2024; 14(7).

PMID: 39064029 PMC: 11278138. DOI: 10.3390/jpm14070775.

Select amino acids recover cytokine-altered ENaC function in human bronchial epithelial cells.

Sasidharan A, Grosche A, Xu X, Kinane T, Angoli D, Vidyasagar S PLoS One. 2024; 19(7):e0307809.

PMID: 39052685 PMC: 11271875. DOI: 10.1371/journal.pone.0307809.

References

Liu X, Gao N, Li M, Xu D, Hou Y, Wang Q . Elevated levels of CD4(+)CD25(+)FoxP3(+) T cells in systemic sclerosis patients contribute to the secretion of IL-17 and immunosuppression dysfunction. PLoS One. 2013; 8(6):e64531. PMC: 3679128. DOI: 10.1371/journal.pone.0064531. View

Oldenhove G, Bouladoux N, Wohlfert E, Hall J, Chou D, Dos Santos L . Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity. 2009; 31(5):772-86. PMC: 2814877. DOI: 10.1016/j.immuni.2009.10.001. View

Huehn J, Hamann A . Homing to suppress: address codes for Treg migration. Trends Immunol. 2005; 26(12):632-6. DOI: 10.1016/j.it.2005.10.001. View

Fontenot J, Rudensky A . A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol. 2005; 6(4):331-7. DOI: 10.1038/ni1179. View

Vignali D, Collison L, Workman C . How regulatory T cells work. Nat Rev Immunol. 2008; 8(7):523-32. PMC: 2665249. DOI: 10.1038/nri2343. View

Lee Y, Awasthi A, Yosef N, Quintana F, Xiao S, Peters A . Induction and molecular signature of pathogenic TH17 cells. Nat Immunol. 2012; 13(10):991-9. PMC: 3459594. DOI: 10.1038/ni.2416. View

Ciofani M, Madar A, Galan C, Sellars M, Mace K, Pauli F . A validated regulatory network for Th17 cell specification. Cell. 2012; 151(2):289-303. PMC: 3503487. DOI: 10.1016/j.cell.2012.09.016. 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

Hoffmann P, Eder R, Boeld T, Doser K, Piseshka B, Andreesen R . Only the CD45RA+ subpopulation of CD4+CD25high T cells gives rise to homogeneous regulatory T-cell lines upon in vitro expansion. Blood. 2006; 108(13):4260-7. DOI: 10.1182/blood-2006-06-027409. View

10.

Dong C . TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008; 8(5):337-48. DOI: 10.1038/nri2295. View

11.

Matusevicius D, Kivisakk P, He B, Kostulas N, Ozenci V, Fredrikson S . Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult Scler. 1999; 5(2):101-4. DOI: 10.1177/135245859900500206. View

12.

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

13.

Machnik A, Dahlmann A, Kopp C, Goss J, Wagner H, van Rooijen N . Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive enhancer binding protein/vascular endothelial growth factor C expression and induces salt-sensitive hypertension in rats. Hypertension. 2010; 55(3):755-61. DOI: 10.1161/HYPERTENSIONAHA.109.143339. View

14.

Borsellino G, Kleinewietfeld M, Di Mitri D, Sternjak A, Diamantini A, Giometto R . Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 2007; 110(4):1225-32. DOI: 10.1182/blood-2006-12-064527. View

15.

Feng T, Cao A, Weaver C, Elson C, Cong Y . Interleukin-12 converts Foxp3+ regulatory T cells to interferon-γ-producing Foxp3+ T cells that inhibit colitis. Gastroenterology. 2011; 140(7):2031-43. PMC: 3109200. DOI: 10.1053/j.gastro.2011.03.009. View

16.

Li Y, Wang H, Long Y, Lu Z, Hu X . Increased memory Th17 cells in patients with neuromyelitis optica and multiple sclerosis. J Neuroimmunol. 2011; 234(1-2):155-60. DOI: 10.1016/j.jneuroim.2011.03.009. View

17.

Duarte J, Zelenay S, Bergman M, Martins A, Demengeot J . Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions. Eur J Immunol. 2009; 39(4):948-55. DOI: 10.1002/eji.200839196. View

18.

Hirota K, Duarte J, Veldhoen M, Hornsby E, Li Y, Cua D . Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol. 2011; 12(3):255-63. PMC: 3040235. DOI: 10.1038/ni.1993. View

19.

Haas J, Fritzsching B, Trubswetter P, Korporal M, Milkova L, Fritz B . Prevalence of newly generated naive regulatory T cells (Treg) is critical for Treg suppressive function and determines Treg dysfunction in multiple sclerosis. J Immunol. 2007; 179(2):1322-30. DOI: 10.4049/jimmunol.179.2.1322. View

20.

Greer J, Pender M . Myelin proteolipid protein: an effective autoantigen and target of autoimmunity in multiple sclerosis. J Autoimmun. 2008; 31(3):281-7. DOI: 10.1016/j.jaut.2008.04.018. View