IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease

• DOI: 10.1038/s41467-017-00838-4
• Publication Date: 2017-09-22T10:58:37Z
• Authors: Ivy M. Dambuza; Chang He; Jin Kyeong Choi; Cheng-Rong Yu; Renxi Wang; Mary J. Mattapallil; Paul T. Wingfield; Rachel R. Caspi; Charles E. Egwuagu
• Keywords: 0301 basic medicine; Knockout; T-Lymphocytes; Science; 610; Inbred C57BL; T-Lymphocytes, Regulatory; Article; Interleukin-12 Subunit p35; Autoimmune Diseases; Interleukin-10/metabolism; Uveitis; Mice; 03 medical and health sciences; Th17 Cells/immunology; Animals; QR180 Immunology; Interleukin-12 Receptor beta 2 Subunit; Interleukin-12 Subunit p35/metabolism; Cell Proliferation; Immunosuppression Therapy; Mice, Knockout; B-Lymphocytes; B-Lymphocytes, Regulatory; Q; Uveitis/immunology; Regulatory/metabolism; Interleukin-10; 3. Good health; Mice, Inbred C57BL; Autoimmune Diseases/immunology; Interleukin-12 Receptor beta 2 Subunit/metabolism; QR180; Th17 Cells; Regulatory/immunology; Protein Multimerization; Immunosuppression

Abstract Interleukin 35 (IL-35) is a heterodimeric cytokine composed of IL-12p35 and Ebi3 subunits. IL-35 suppresses autoimmune diseases while preventing host defense to infection promoting tumor growth metastasis by converting resting B T cells into IL-10-producing IL-35-producing regulatory (Breg) (Treg) cells. Despite sharing the subunit, IL-12 (IL-12p35/IL-12p40) promotes inflammatory responses whereas (IL-12p35/Ebi3) induces responses, suggesting that may have unknown intrinsic immune-regulatory functions regulated its partner. Here we show subunit has immunoregulatory hitherto attributed IL-35. lymphocyte proliferation, expansion IL-10-expressing IL-35-expressing ameliorates uveitis in mice antagonizing pathogenic Th17 responses. Recapitulation essential immunosuppressive activities indicates be utilized for vivo Breg autologous cell immunotherapy. Furthermore, our data suggest other single chain subunits might exploited treat diseases.