Journal Article Ppublish 3 citations
PubMed: 38381001 DOI: 10.4049/jimmunol.2200916
IL-33 Induces Cellular and Exosomal miR-146a Expression as a Feedback Inhibitor of Mast Cell Function.
J Immunol 212(8):1277-1286
Authors: Marcela T Taruselli, Amina Abdul Qayum, Daniel Abebayehu, Heather L Caslin, Jordan M Dailey, Aditya Kotha, Jason R Burchett, Sydney A Kee, Tania D Maldonado, Boyang Ren, Wei Chao, Lin Zou, Tamara T Haque, David Straus, John J Ryan
Affiliations
- Department of Biology, Virginia Commonwealth University, Richmond, VA.
- Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD.
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.
MeSH
Cytokines, Cells, Feedback, Interleukin-33, Th2 Cells, Asthma, Mast Cells, Plasma