白细胞介素33
基因剔除小鼠
肥大细胞
细胞生物学
细胞因子
小RNA
信号转导
炎症
免疫学
调节器
受体
生物
白细胞介素
生物化学
基因
作者
Marcela T. Taruselli,Amina Abdul Qayum,Daniel Abebayehu,Heather L. Caslin,Jordan Dailey,Aditya Kotha,Jason Burchett,Sydney Ann Kee,Tania D. Maldonado,Boyang Ren,Wei Chao,Lin Zou,Tamara T. Haque,David B. Straus,John Ryan
标识
DOI:10.4049/jimmunol.2200916
摘要
Abstract IL-33 is an inflammatory cytokine that promotes allergic disease by activating group 2 innate lymphoid cells, Th2 cells, and mast cells. IL-33 is increased in asthmatics, and its blockade suppresses asthma-like inflammation in mouse models. Homeostatic control of IL-33 signaling is poorly understood. Because the IL-33 receptor, ST2, acts via cascades used by the TLR family, similar feedback mechanisms may exist. MicroRNA (miR)-146a is induced by LPS-mediated TLR4 signaling and serves as a feedback inhibitor. Therefore, we explored whether miR-146a has a role in IL-33 signaling. IL-33 induced cellular and exosomal miR-146a expression in mouse bone marrow–derived mast cells (BMMCs). BMMCs transfected with a miR-146a antagonist or derived from miR-146a knockout mice showed enhanced cytokine expression in response to IL-33, suggesting that miR-146a is a negative regulator of IL-33–ST2 signaling. In vivo, miR-146a expression in plasma exosomes was elevated after i.p. injection of IL-33 in wild-type but not mast cell–deficient KitW-sh/W-sh mice. Finally, KitW-sh/W-sh mice acutely reconstituted with miR-146a knockout BMMCs prior to IL-33 challenge had elevated plasma IL-6 levels compared with littermates receiving wild-type BMMCs. These results support the hypothesis that miR-146a is a feedback regulator of IL-33–mediated mast cell functions associated with allergic disease.
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