Induction of Regulatory Tr1 Cells and Inhibition of T(H)17 Cells by IL-27

Overview

Journal Semin Immunol

Specialty Allergy & Immunology

Date 2011 Sep 7

PMID 21893418

Citations 85

Authors

Caroline Pot

Lionel Apetoh

Amit Awasthi

Vijay K Kuchroo

Affiliations

Soon will be listed here.

Abstract

Accumulating evidence indicates that IL-27, a member of the IL-12 family of cytokines, alleviates the severity of autoimmune diseases in both mice and men. The IL-27-induced activation of signal transducer and activator of transcription (Stat)1 and Stat3 promotes the generation of IL-10- producing type 1 regulatory T (Tr1) cells that inhibit effector T cells. In addition, IL-27 also suppresses the development of pathogenic IL-17-producing CD4(+) T cells (T(H)17) cells suggesting that pharmacological manipulations of IL-27 signaling pathway could be exploited therapeutically in regulating tissue inflammation. Here, we review how IL-27 controls inflammation through the regulation of Tr1 and T(H)17 responses.

Citing Articles

Oral SARS-CoV-2 Infection and Risk for Long Covid.

Schwartz J, Capistrano K, Hussein H, Hafedi A, Shukla D, Naqvi A Rev Med Virol. 2025; 35(2):e70029.

PMID: 40074704 PMC: 11903386. DOI: 10.1002/rmv.70029.

T-follicular helper cells are epigenetically poised to transdifferentiate into T-regulatory type 1 cells.

Garnica J, Sole P, Yamanouchi J, Moro J, Mondal D, Fandos C Elife. 2024; 13.

PMID: 39576679 PMC: 11584177. DOI: 10.7554/eLife.97665.

Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner.

Imamichi T, Chen Q, Sowrirajan B, Yang J, Laverdure S, Marquez M PLoS One. 2023; 18(11):e0287829.

PMID: 37910521 PMC: 10619827. DOI: 10.1371/journal.pone.0287829.

Evolutionarily conserved IL-27β enhances Th1 cells potential by triggering the JAK1/STAT1/T-bet axis in Nile tilapia.

Geng M, Li K, Ai K, Liang W, Yang J, Wei X Fish Shellfish Immunol Rep. 2023; 4:100087.

PMID: 36873098 PMC: 9978509. DOI: 10.1016/j.fsirep.2023.100087.

Interleukin 27 is a novel cytokine with anti-inflammatory effects against spondyloarthritis through the suppression of Th17 responses.

Jouhault Q, Cherqaoui B, Jobart-Malfait A, Glatigny S, Lauraine M, Hulot A Front Immunol. 2023; 13:1072420.

PMID: 36818477 PMC: 9933703. DOI: 10.3389/fimmu.2022.1072420.

References

Wildin R, Ramsdell F, Peake J, Faravelli F, Casanova J, Buist N . X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001; 27(1):18-20. DOI: 10.1038/83707. View

Troy A, Zaph C, Du Y, Taylor B, Guild K, Hunter C . IL-27 regulates homeostasis of the intestinal CD4+ effector T cell pool and limits intestinal inflammation in a murine model of colitis. J Immunol. 2009; 183(3):2037-44. PMC: 2821569. DOI: 10.4049/jimmunol.0802918. View

Rosas L, Satoskar A, Roth K, Keiser T, Barbi J, Hunter C . Interleukin-27R (WSX-1/T-cell cytokine receptor) gene-deficient mice display enhanced resistance to leishmania donovani infection but develop severe liver immunopathology. Am J Pathol. 2006; 168(1):158-69. PMC: 1592683. DOI: 10.2353/ajpath.2006.050013. 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

Zhang Z, Zheng M, Bindas J, Schwarzenberger P, Kolls J . Critical role of IL-17 receptor signaling in acute TNBS-induced colitis. Inflamm Bowel Dis. 2006; 12(5):382-8. DOI: 10.1097/01.MIB.0000218764.06959.91. View

Pot C, Apetoh L, Awasthi A, Kuchroo V . Molecular pathways in the induction of interleukin-27-driven regulatory type 1 cells. J Interferon Cytokine Res. 2010; 30(6):381-8. PMC: 2964360. DOI: 10.1089/jir.2010.0047. View

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

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

Pot C, Jin H, Awasthi A, Liu S, Lai C, Madan R . Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. J Immunol. 2009; 183(2):797-801. PMC: 2768608. DOI: 10.4049/jimmunol.0901233. View

10.

Conti H, Shen F, Nayyar N, Stocum E, Sun J, Lindemann M . Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med. 2009; 206(2):299-311. PMC: 2646568. DOI: 10.1084/jem.20081463. View

11.

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

12.

Chae S, Li C, Kim K, Yang J, Zhang Q, Lee Y . Identification of polymorphisms in human interleukin-27 and their association with asthma in a Korean population. J Hum Genet. 2007; 52(4):355-361. DOI: 10.1007/s10038-007-0123-8. View

13.

Lang R, Pauleau A, Parganas E, Takahashi Y, Mages J, Ihle J . SOCS3 regulates the plasticity of gp130 signaling. Nat Immunol. 2003; 4(6):546-50. DOI: 10.1038/ni932. 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.

Honda K, Nakamura K, Matsui N, Takahashi M, Kitamura Y, Mizutani T . T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis. Inflamm Bowel Dis. 2005; 11(12):1044-52. DOI: 10.1097/01.mib.0000191611.05466.1f. View

16.

Bacchetta R, Bigler M, Touraine J, Parkman R, Tovo P, Abrams J . High levels of interleukin 10 production in vivo are associated with tolerance in SCID patients transplanted with HLA mismatched hematopoietic stem cells. J Exp Med. 1994; 179(2):493-502. PMC: 2191349. DOI: 10.1084/jem.179.2.493. View

17.

Yoshimoto T, Yoshimoto T, Yasuda K, Mizuguchi J, Nakanishi K . IL-27 suppresses Th2 cell development and Th2 cytokines production from polarized Th2 cells: a novel therapeutic way for Th2-mediated allergic inflammation. J Immunol. 2007; 179(7):4415-23. DOI: 10.4049/jimmunol.179.7.4415. View

18.

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

19.

Moisan J, Grenningloh R, Bettelli E, Oukka M, Ho I . Ets-1 is a negative regulator of Th17 differentiation. J Exp Med. 2007; 204(12):2825-35. PMC: 2118518. DOI: 10.1084/jem.20070994. View

20.

Coquet J, Chakravarti S, Smyth M, Godfrey D . Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis. J Immunol. 2008; 180(11):7097-101. DOI: 10.4049/jimmunol.180.11.7097. View