Cyclooxygenase-1 Regulates the Development of Follicular Th Cells via Prostaglandin E2
Cyclooxygenase-1 Regulates the Development of Follicular Th Cells via Prostaglandin E2
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Cyclooxygenase-1 通过前列腺素 E-2 调节滤泡 Th 细胞的发育
DOI：
10.4049/jimmunol.1801674
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发表时间：
2019-08-15
影响因子：
4.4
通讯作者：
Zhou, Jie
中科院分区：
文献类型：
--
作者：
Liu, Ting;Yang, Qiong;Zhou, Jie
环氧合酶（考克斯）-1是花生四烯酸转化为前列腺素（PGs）的关键酶之一，不仅在心血管系统中起重要作用，而且在免疫系统中也起重要作用。已发现考克斯-1调节早期B细胞分化、生发中心形成和B细胞的Ab产生。然而，考克斯-1介导的B细胞活化的潜在机制仍然没有完全理解。在本研究中，我们报道了考克斯-1是一个潜在的调节卵泡Th（T-FH）细胞的发育。考克斯-/-缺陷（考克斯-1（-/-））小鼠在流感感染或用钥孔血蓝蛋白免疫后显示出T-FH细胞的显著减少，这导致生发中心反应的严重损害。我们进一步证明，考克斯-1衍生的PGE（2）通过与其受体EP 2/EP 4结合，代表了潜在的机制。给予EP 2/EP 4激动剂或PGE（2）几乎完全挽救了考克斯-1（-/-）小鼠中缺陷T-FH细胞的生成。综上所述，我们的观察结果表明，考克斯-1在T-FH细胞的发展中起着重要的作用。
Cyclooxygenase (COX)-1, one of the critical enzymes required for the conversion of arachidonic acid to PGs, has been demonstrated to play an important role not only in the cardiovascular system but also in the immune system. COX-1 has been found to regulate early B cell differentiation, germinal center formation, and Ab production of B cells. However, the underlying mechanisms of COX-1-mediated B cell activation remains not fully understood. In this study, we reported that COX-1 is a potential regulator for the development of follicular Th (T-FH) cells. COX-/-deficient (COX-1(-/-)) mice displayed a significant reduction of T-FH cells upon influenza infection or immunization with keyhole limpet hemocyanin, which led to a severe impairment of germinal center responses. We further demonstrated that COX-1-derived PGE(2), via binding with its receptors EP2/EP4, represents the underlying mechanism. The administration of EP2/EP4 agonists or PGE(2) almost completely rescued the defective T-FH cell generation in COX-1(-/- )mice. Taken together, our observations indicate that COX-1 plays an important role in the development of T-FH cells.