Insulin-regulated aminopeptidase contributes to setting the intensity of FcR-mediated inflammation - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Frontiers in Immunology Year : 2022

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-inactivating phosphorylation on Ser 591 that controls Syk activity was decreased. Ex-vivo cell profiling after FcγR-triggered anaphylaxis confirmed decreased phosphorylation of both Syk Y519/520 and SHP-1 S591 in IRAP-deficient neutrophils and monocytes. Thus, IRAP-positive endosomal compartments, in promoting inhibition of SHP-1 during FcR signaling, control the extent of phosphorylation events at the plasma membrane and contribute to setting the intensity of immune-complex triggered inflammatory diseases.
Fichier principal
Vignette du fichier
fimmu-13-1029759.pdf (13.7 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Licence : CC BY - Attribution

Dates and versions

inserm-03998813 , version 1 (21-02-2023)

Identifiers

Cite

Manuela Bratti, Shamila Vibhushan, Cyril Longé, Despoina Koumantou, Gaël Ménasché, et al.. Insulin-regulated aminopeptidase contributes to setting the intensity of FcR-mediated inflammation. Frontiers in Immunology, 2022, 13, pp.1029759. ⟨10.3389/fimmu.2022.1029759⟩. ⟨inserm-03998813⟩
23 View
21 Download

Altmetric

Share

Gmail Facebook X LinkedIn More