title: IL-35 stimulation of CD39+ regulatory T cells confers protection against collagen II-induced arthritis via the production of IL-10.
abstract: IL-35 is produced by regulatory T cells, and this novel cytokine can downregulate Th17 cell development and inhibit autoimmune inflammation. In this work, an rIL-35, as a single-chain fusion between murine IL-12p35 and EBV-induced gene 3, was expressed in yeast. This rIL-35 inhibited OVA-specific cellular and Ab responses in OVA-challenged recipients of DO11.10 CD4+ T cells. Likewise, IL-35 inhibited clinical manifestation of collagen-induced arthritis or could cease further disease exacerbation upon initiation of IL-35 treatment. Exogenous IL-35 treatments suppressed Th1 and Th17 cells and promoted CD39 expression by CD4+ T cells. Sorted CD25-CD39+CD4+ T cells from IL-35-treated mice produced IL-10 and, upon adoptive transfer, were sufficiently potent to inhibit subsequent development of inflammation in mice with collagen-induced arthritis, whereas sorted CD25+CD39+CD4+ T cells showed reduced potency. IL-35 treatments of IL-10-/- mice failed to induce protective CD39+CD4+ T cells, demonstrating the effector role of IL-10 by IL-35 immunosuppression.
authors.affiliation: Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Kochetkova
authors.forename: Sarah
authors.initials: S
authors.lastname: Golden
authors.forename: Kathryn
authors.initials: K
authors.lastname: Holderness
authors.forename: Gayle
authors.initials: G
authors.lastname: Callis
authors.forename: David W
authors.initials: DW
authors.lastname: Pascual
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001081:Apyrase / Q000276:immunology / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D053765:Interleukin-12 Subunit p35 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D053765:Interleukin-12 Subunit p35; D011994:Recombinant Proteins; D016753:Interleukin-10; D001081:Apyrase; C067869:CD39 antigen