The Effects of IL-6 on CD4 T Cell Responses

Overview

Journal Clin Immunol

Specialty Allergy & Immunology

Date 2008 Oct 11

PMID 18845487

Citations 233

Authors

Oliver Dienz

Mercedes Rincon

Affiliations

Soon will be listed here.

Abstract

Cytokines have long been known to profoundly influence the adaptive immune response by determining CD4 T cell differentiation. Although IL-6 has been initially characterized as a B cell growth factor and inducer of antibody production research from our lab and others has revealed over the last years that IL-6 also plays a significant role in CD4 T cell differentiation. This review highlights the variety of ways in which IL-6 affects CD4 effector functions and how this may contribute to different types of diseases.

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References

Atreya R, Mudter J, Finotto S, Mullberg J, Jostock T, Wirtz S . Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo. Nat Med. 2000; 6(5):583-8. DOI: 10.1038/75068. View

Ichiyama K, Yoshida H, Wakabayashi Y, Chinen T, Saeki K, Nakaya M . Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat. J Biol Chem. 2008; 283(25):17003-8. DOI: 10.1074/jbc.M801286200. View

Jostock T, Mullberg J, Ozbek S, Atreya R, Blinn G, Voltz N . Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur J Biochem. 2000; 268(1):160-7. DOI: 10.1046/j.1432-1327.2001.01867.x. View

Diehl S, Anguita J, Hoffmeyer A, Zapton T, Ihle J, Fikrig E . Inhibition of Th1 differentiation by IL-6 is mediated by SOCS1. Immunity. 2001; 13(6):805-15. DOI: 10.1016/s1074-7613(00)00078-9. View

Diehl S, Chow C, Weiss L, Palmetshofer A, Twardzik T, Rounds L . Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation. J Exp Med. 2002; 196(1):39-49. PMC: 2194007. DOI: 10.1084/jem.20020026. View

Wurster A, Rodgers V, Satoskar A, Whitters M, Young D, Collins M . Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon gamma-producing Th1 cells. J Exp Med. 2002; 196(7):969-77. PMC: 2194031. DOI: 10.1084/jem.20020620. View

Ozaki K, Spolski R, Feng C, Qi C, Cheng J, Sher A . A critical role for IL-21 in regulating immunoglobulin production. Science. 2002; 298(5598):1630-4. DOI: 10.1126/science.1077002. View

Pasare C, Medzhitov R . Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science. 2003; 299(5609):1033-6. DOI: 10.1126/science.1078231. View

Boulanger M, Chow D, Brevnova E, Garcia K . Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex. Science. 2003; 300(5628):2101-4. DOI: 10.1126/science.1083901. View

10.

Heinrich P, Behrmann I, Haan S, Hermanns H, Muller-Newen G, Schaper F . Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J. 2003; 374(Pt 1):1-20. PMC: 1223585. DOI: 10.1042/BJ20030407. View

11.

Chen W, Jin W, Hardegen N, Lei K, Li L, Marinos N . Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003; 198(12):1875-86. PMC: 2194145. DOI: 10.1084/jem.20030152. View

12.

Chtanova T, Tangye S, Newton R, Frank N, Hodge M, Rolph M . T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J Immunol. 2004; 173(1):68-78. DOI: 10.4049/jimmunol.173.1.68. View

13.

Weissenbach M, Clahsen T, Weber C, Spitzer D, Wirth D, Vestweber D . Interleukin-6 is a direct mediator of T cell migration. Eur J Immunol. 2004; 34(10):2895-906. DOI: 10.1002/eji.200425237. View

14.

Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T . Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature. 1986; 324(6092):73-6. DOI: 10.1038/324073a0. View

15.

Lotz M, Jirik F, Kabouridis P, Tsoukas C, Hirano T, Kishimoto T . B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med. 1988; 167(3):1253-8. PMC: 2188869. DOI: 10.1084/jem.167.3.1253. View

16.

Saito M, Yoshida K, Hibi M, Taga T, Kishimoto T . Molecular cloning of a murine IL-6 receptor-associated signal transducer, gp130, and its regulated expression in vivo. J Immunol. 1992; 148(12):4066-71. View

17.

Mullberg J, Schooltink H, Stoyan T, Gunther M, Graeve L, Buse G . The soluble interleukin-6 receptor is generated by shedding. Eur J Immunol. 1993; 23(2):473-80. DOI: 10.1002/eji.1830230226. View

18.

Ramji D, Vitelli A, Tronche F, Cortese R, Ciliberto G . The two C/EBP isoforms, IL-6DBP/NF-IL6 and C/EBP delta/NF-IL6 beta, are induced by IL-6 to promote acute phase gene transcription via different mechanisms. Nucleic Acids Res. 1993; 21(2):289-94. PMC: 309105. DOI: 10.1093/nar/21.2.289. View

19.

Zhong Z, Wen Z, Darnell Jr J . Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science. 1994; 264(5155):95-8. DOI: 10.1126/science.8140422. View

20.

Horiuchi S, Koyanagi Y, Zhou Y, Miyamoto H, Tanaka Y, Waki M . Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism. Eur J Immunol. 1994; 24(8):1945-8. DOI: 10.1002/eji.1830240837. View