ORMDL3 Functions as a Negative Regulator of Antigen-Mediated Mast Cell Activation via an ATF6-UPR-Autophagy-Dependent Pathway.

ABSTRACT: Antigen (Ag)-mediated mast cell activation plays a critical role in the immunopathology of IgE-dependent allergic diseases. Restraining the signaling cascade that regulates the release of mast cell-derived inflammatory mediators is an attractive therapeutic strategy to treat allergic diseases. Orosomucoid-like-3 (ORMDL3) regulates the endoplasmic reticulum stress (ERS)-induced unfolded protein response (UPR) and autophagy. Although ERS/UPR/autophagy pathway is crucial in Ag-induced mast cell activation, it is unknown whether ORMDL3 regulates the ERS/UPR/autophagy pathway during mast cell activation. In this study, we found that ORMDL3 expression was downregulated in Ag-activated MC/9 cells. Overexpression of ORMDL3 significantly inhibited degranulation, and cytokine/chemokine production, w

SUBMITTER: Li J 

PROVIDER: S-EPMC7933793 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature