Ebi3 promotes T- and B-cell division and differentiation via STAT3
Ebi3 promotes T- and B-cell division and differentiation via STAT3
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Ebi3 通过 STAT3 促进 T 细胞和 B 细胞分裂和分化
DOI：
10.1016/j.molimm.2019.01.009
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发表时间：
2019-03-01
影响因子：
3.6
通讯作者：
Wang, Renxi
中科院分区：
文献类型：
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作者：
Ma, Ning;Fang, Ying;Wang, Renxi
IL-27 （p28/Ebi3）和IL-35 （p35/Ebi3）虽然共享同一个亚基Ebi3，但具有不同的生物学功能，提示Ebi3亚基可能具有载体功能。我们的数据表明，活化的T细胞和B细胞有效地上调了Ebi3的表达。此外，Ebi3有效促进了Th1、Th17和Treg极化条件下分别诱导的辅助性t1 （Th1）、Th17和Foxp3（+）调节性T （Treg）细胞的T细胞活化和分化。自然地，Ebi3可以促进LPS诱导的b细胞活化和CD138（+）浆细胞（PC）的产生。相反，中和抗ebi3抗体可以显著抑制Th1、Th17、Treg极化条件和LPS诱导的T/ b细胞活化和Th1、Th17、Tregs和PC的产生。此外，我们发现Ebi3在CD4(+)T细胞和B细胞中诱导STAT3激活具有时间依赖性。相反，STAT3（-/-）有效地降低了Ebi3的表达和Th1、Th17、Tregs和浆细胞的产生。最后，我们发现gp130介导而不是IL-27R α介导ebi3诱导的STAT3激活。这些结果表明Ebi3通过gp130-STAT3信号通路促进Th细胞和b细胞分化。因此，自分泌的Ebi3可能在Th和B细胞的分化中发挥重要作用，从而在感染、炎症和自身免疫性疾病中发挥重要作用。
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.