Role of Th1 and Th17 Cells in Organ-specific Autoimmunity

Overview

Journal J Autoimmun

Specialty Allergy & Immunology

Date 2008 May 27

PMID 18502610

Citations 203

Authors

Valerie Dardalhon

Thomas Korn

Vijay K Kuchroo

Ana C Anderson

Affiliations

Soon will be listed here.

Abstract

CD4(+) IFN-gamma-producing Th1 cells have long been associated with the pathogenesis of many organ-specific autoimmune diseases; however, the observation of disease in mice deficient in molecules involved in Th1 cell differentiation raised the possibility that other effector T cells were responsible for inducing autoimmunity. Recently, a new CD4(+) effector T cell subset that produces IL-17 (Th17) has emerged. The fact that Th17 cells are highly auto-pathogenic has fueled a debate as to what role, if any, Th1 cells play in the induction of tissue inflammation and autoimmune disease. This review will discuss the respective roles of the Th1 and Th17 subsets in organ-specific autoimmunity.

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References

Pflanz S, Timans J, Cheung J, Rosales R, Kanzler H, Gilbert J . IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity. 2002; 16(6):779-90. DOI: 10.1016/s1074-7613(02)00324-2. View

Aarvak T, Chabaud M, Miossec P, Natvig J . IL-17 is produced by some proinflammatory Th1/Th0 cells but not by Th2 cells. J Immunol. 1999; 162(3):1246-51. View

Nicholson L, Kuchroo V . Manipulation of the Th1/Th2 balance in autoimmune disease. Curr Opin Immunol. 1996; 8(6):837-42. DOI: 10.1016/s0952-7915(96)80013-6. View

Tran E, Prince E, Owens T . IFN-gamma shapes immune invasion of the central nervous system via regulation of chemokines. J Immunol. 2000; 164(5):2759-68. DOI: 10.4049/jimmunol.164.5.2759. View

Renno T, Krakowski M, Piccirillo C, Lin J, Owens T . TNF-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis. Regulation by Th1 cytokines. J Immunol. 1995; 154(2):944-53. View

Rouvier E, Luciani M, Mattei M, Denizot F, Golstein P . CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol. 1993; 150(12):5445-56. View

Germann T, Hess H, Szeliga J, Rude E . Characterization of the adjuvant effect of IL-12 and efficacy of IL-12 inhibitors in type II collagen-induced arthritis. Ann N Y Acad Sci. 1996; 795:227-40. DOI: 10.1111/j.1749-6632.1996.tb52672.x. View

Bettelli E, Sullivan B, Szabo S, Sobel R, Glimcher L, Kuchroo V . Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med. 2004; 200(1):79-87. PMC: 2213316. DOI: 10.1084/jem.20031819. View

Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M . Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science. 2007; 317(5835):256-60. DOI: 10.1126/science.1145697. View

10.

Matthys P, Vermeire K, Mitera T, Heremans H, Huang S, Billiau A . Anti-IL-12 antibody prevents the development and progression of collagen-induced arthritis in IFN-gamma receptor-deficient mice. Eur J Immunol. 1998; 28(7):2143-51. DOI: 10.1002/(SICI)1521-4141(199807)28:07<2143::AID-IMMU2143>3.0.CO;2-C. View

11.

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

12.

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

13.

Mathur A, Chang H, Zisoulis D, Kapur R, Belladonna M, Kansas G . T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype. Blood. 2006; 108(5):1595-601. PMC: 1895507. DOI: 10.1182/blood-2006-04-015016. View

14.

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

15.

Gutcher I, Urich E, Wolter K, Prinz M, Becher B . Interleukin 18-independent engagement of interleukin 18 receptor-alpha is required for autoimmune inflammation. Nat Immunol. 2006; 7(9):946-53. DOI: 10.1038/ni1377. View

16.

Aggarwal S, Gurney A . IL-17: prototype member of an emerging cytokine family. J Leukoc Biol. 2002; 71(1):1-8. View

17.

Khattri R, Cox T, Yasayko S, Ramsdell F . An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol. 2003; 4(4):337-42. DOI: 10.1038/ni909. View

18.

Rangachari M, Mauermann N, Marty R, Dirnhofer S, Kurrer M, Komnenovic V . T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17. J Exp Med. 2006; 203(8):2009-19. PMC: 2118365. DOI: 10.1084/jem.20052222. View

19.

Hori S, Nomura T, Sakaguchi S . Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003; 299(5609):1057-61. DOI: 10.1126/science.1079490. View

20.

Ben-Nun A, Cohen I . Vaccination against autoimmune encephalomyelitis (EAE): attenuated autoimmune T lymphocytes confer resistance to induction of active EAE but not to EAE mediated by the intact T lymphocyte line. Eur J Immunol. 1981; 11(11):949-52. DOI: 10.1002/eji.1830111119. View