Insulin-regulated aminopeptidase contributes to setting the intensity of FcR-mediated inflammation.

ABSTRACT: The function of intracellular trafficking in immune-complex triggered inflammation remains poorly understood. Here, we investigated the role of Insulin-Regulated Amino Peptidase (IRAP)-positive endosomal compartments in Fc receptor (FcR)-induced inflammation. Less severe FcγR-triggered arthritis, active systemic anaphylaxis and FcεRI-triggered passive systemic anaphylaxis were observed in IRAP-deficient versus wild-type mice. In mast cells FcεRI stimulation induced rapid plasma membrane recruitment of IRAP-positive endosomes. IRAP-deficient cells exhibited reduced secretory responses, calcium signaling and activating Syk^Y519/520 phosphorylation albeit receptor tyrosine phosphorylation on β and γ subunits was not different. By contrast, in the absence of IRAP, SHP1-inactiv

SUBMITTER: Bratti M 

PROVIDER: S-EPMC9647545 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature