%0 Journal Article %T Insulin-regulated aminopeptidase contributes to setting the intensity of FcR-mediated inflammation %+ Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)) %+ Laboratoire d'Excellence Inflamex [Paris] %+ Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163) %+ Adaptateurs de signalisation en hématologie (ASIH) %+ UFR Santé, Médecine et Biologie Humaine (UFR SMBH) %+ Université Mohammed VI Polytechnique [Ben Guerir] (UM6P) %A Bratti, Manuela %A Vibhushan, Shamila %A Longé, Cyril %A Koumantou, Despoina %A Ménasché, Gaël %A Benhamou, Marc %A Varin-Blank, Nadine %A Blank, Ulrich %A Saveanu, Loredana %A Ben Mkaddem, Sanae %< avec comité de lecture %@ 1664-3224 %J Frontiers in Immunology %I Frontiers %V 13 %P 1029759 %8 2022-10-27 %D 2022 %R 10.3389/fimmu.2022.1029759 %M 36389775 %K Fc receptors %K inflammation %K insulin-regulated aminopeptidase %K intracellular trafficking %K signaling. %K Fc receptors %Z Life Sciences [q-bio]Journal articles %X 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. %G English %2 https://inserm.hal.science/inserm-03998813/document %2 https://inserm.hal.science/inserm-03998813/file/fimmu-13-1029759.pdf %L inserm-03998813 %U https://inserm.hal.science/inserm-03998813 %~ INSERM %~ UNIV-PARIS13 %~ CNRS %~ ASIH %~ SORBONNE-PARIS-NORD %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SANTE %~ ANR %~ SIMHEL