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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

Niedbala, Wanda, Wei, Xiao-Qing, Cai, Beilei, Hueber, Axel J., Leung, Bernard P., McInnes, Iain and Liew, Foo Yew 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. 10.1002/eji.200737810

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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 whichwe nowcall 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-c 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 antigenpresenting 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-c 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: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Subjects: Q Science > QR Microbiology > QR180 Immunology
Uncontrolled Keywords: Arthritis ; Cytokines ; IL-35 ; Regulatory T cells ; Th17 cells
Publisher: Wiley-Blackwell
ISSN: 0014-2980
Last Modified: 04 Jun 2017 04:15
URI: http://orca-mwe.cf.ac.uk/id/eprint/35633

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