IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells

Cai, B., Hueber, A. J., Leung, B. P., Liew, F. Y., McInnes, I. B. , Niedbala, W. and Wei, X.-q. (2007) IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. European Journal of Immunology, 37(11), pp. 3021-3029. (doi:10.1002/eji.200737810)

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Publisher's URL: http://dx.doi.org/10.1002/eji.200737810

Abstract

Epstein-Barr virus-induced gene 3 (EBI3) and the p35 subunit of IL-12 have been reported to form a heterodimeric hematopoietin in human and mouse. We have constructed a heterodimeric protein covalently linking EBI3 and p35, to form a novel cytokine which we now call IL-35. The Fc fusion protein of IL-35 induced proliferation of murine CD4+CD25+ and CD4+CD25 T cells when stimulated with immobilized anti-CD3 and anti-CD28 antibodies in vitro. The IL-35-expanded CD4+CD25+ T cell population expressed Foxp3 and produced elevated levels of IL-10, whereas the IL-35-induced CD4+CD25– T cells produced IFN-γ but not IL-4. The in vitro expanded CD4+CD25+ T cells retained their suppressive functions against CD4+CD25 effector cells. Furthermore, when cultured with soluble anti-CD3 antibody and antigen-presenting cells, IL-35 suppressed the proliferation of CD4+CD25– effector cells. Moreover, IL-35 inhibited the differentiation of Th17 cells in vitro. In vivo, IL-35 effectively attenuated established collagen-induced arthritis in mice, with concomitant suppression of IL-17 production but enhanced IFN-γ synthesis. Thus, IL-35 is a novel anti-inflammatory cytokine suppressing the immune response through the expansion of regulatory T cells and suppression of Th17 cell development.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Liew, Professor Foo and Niedbala, Dr Wanda and Hueber, Dr Axel and Cai, Ms Beilei and Leung, Dr Bernard
Authors: Cai, B., Hueber, A. J., Leung, B. P., Liew, F. Y., McInnes, I. B., Niedbala, W., and Wei, X.-q.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:European Journal of Immunology
Journal Abbr.:Eur. J. Immunol.
Publisher:Wiley-Blackwell Publishing
ISSN:0014-2980
ISSN (Online):1521-4141
Published Online:14 September 2007
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
380241Toll-like receptors on T cellsFoo LiewMedical Research Council (MRC)G9818261Infection Immunity and Inflammation Medicine