Although sharing the same subunit Ebi3, IL-27 (p28/Ebi3) and IL-35 (p35/Ebi3) have different biological functions, suggesting that Ebi3 subunit may functions as a carrier. Our data demonstrated that activated T cells and B cells effectively up-regulated Ebi3 expression. In addition, Ebi3 effectively promoted T-cell activation and the differentiation of helper T 1 (Th1), Th17, and Foxp3(+) regulatory T (Treg) cells induced by Th1, Th17, and Treg polarizing condition, respectively. Naturally, Ebi3 could promote B-cell activation and the production of CD138(+) plasma cells (PC) induced by LPS. Conversely, neutralizing anti-Ebi3 antibody could significantly suppress T/B-cell activation and production of Th1, Th17, Tregs, and PC induced by Th1, Th17, Treg polarizing condition, and LPS, respectively. Furthermore, we found that Ebi3 time-dependently induced STAT3 activation in CD4(+)T cells and B cells. Conversely, STAT3(-/-) effectively reduced Ebi3 expression and the production of Th1, Th17, Tregs, and plasma cells. Finally, we showed that gp130 but not IL-27R alpha mediates Ebi3-induced STAT3 activation. These results suggest that Ebi3 promotes Th- and B-cell differentiation via gp130-STAT3 signaling pathway. Thus, autocrine Ebi3 may play an important role in the differentiation of Th and B cells and thus in infection, inflammation, and autoimmune disorders.
[1]Jilin Univ, Hosp 1, Dept Rheumatol, Changchun 130021, Jilin, Peoples R China.
[2]Inst Basic Med Sci, Immunol Lab, POB 130 3,Taiping Rd 27, Beijing 100850, Peoples R China.
[3]Xinjiang Univ, Coll Life Sci & Technol, Urumqi 830046, Xinjiang, Peoples R China.
[4]Chinese Peoples Liberat Army Gen Hosp, Dept Geriatr Hematol, Beijing 100853, Peoples R China.
[5]Staidson Beijing Biopharmaceut Co Ltd, Beijing 100176, Peoples R China.
[6]Jilin Univ, Dept Oral & Maxillofacial Surg, Hosp Stomatol, Xinming Str 71, Changchun 130021, Jilin, Peoples R China.
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