1. Interleukin-35 induces regulatory B cells that suppress autoimmune disease.
- Author
-
Wang, Ren-Xi, Yu, Cheng-Rong, Dambuza, Ivy M, Mahdi, Rashid M, Dolinska, Monika B, Sergeev, Yuri V, Wingfield, Paul T, Kim, Sung-Hye, and Egwuagu, Charles E
- Subjects
- *
B cells , *AUTOIMMUNE diseases , *INTERLEUKIN-1 , *UVEITIS , *EYE inflammation - Abstract
Interleukin-10 (IL-10)-producing regulatory B (Breg) cells suppress autoimmune disease, and increased numbers of Breg cells prevent host defense to infection and promote tumor growth and metastasis by converting resting CD4+ T cells to regulatory T (Treg) cells. The mechanisms mediating the induction and development of Breg cells remain unclear. Here we show that IL-35 induces Breg cells and promotes their conversion to a Breg subset that produces IL-35 as well as IL-10. Treatment of mice with IL-35 conferred protection from experimental autoimmune uveitis (EAU), and mice lacking IL-35 (p35 knockout (KO) mice) or defective in IL-35 signaling (IL-12Rβ2 KO mice) produced less Breg cells endogenously or after treatment with IL-35 and developed severe uveitis. Adoptive transfer of Breg cells induced by recombinant IL-35 suppressed EAU when transferred to mice with established disease, inhibiting pathogenic T helper type 17 (TH17) and TH1 cells while promoting Treg cell expansion. In B cells, IL-35 activates STAT1 and STAT3 through the IL-35 receptor comprising the IL-12Rβ2 and IL-27Rα subunits. As IL-35 also induced the conversion of human B cells into Breg cells, these findings suggest that IL-35 may be used to induce autologous Breg and IL-35+ Breg cells and treat autoimmune and inflammatory disease. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF