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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
Author(s) -
Niedbala Wanda,
Wei Xiaoqing,
Cai Beilei,
Hueber Axel J,
Leung Bernard P.,
McInnes Iain B.,
Liew Foo Y.
Publication year - 2007
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200737810
Subject(s) - il 2 receptor , biology , cytokine , interleukin 21 , foxp3 , microbiology and biotechnology , cd28 , t cell , immune system , immunology
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.