PMID- 27999175
OWN - NLM
STAT- MEDLINE
DCOM- 20171120
LR  - 20210102
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 9
IP  - 459
DP  - 2016 Dec 20
TI  - Trans-inhibition of activation and proliferation signals by Fc receptors in mast 
      cells and basophils.
PG  - ra126
LID - 10.1126/scisignal.aag1401 [doi]
AB  - Allergic and autoimmune inflammation are associated with the activation of mast 
      cells and basophils by antibodies against allergens or auto-antigens, 
      respectively. Both cell types express several receptors for the Fc portion of 
      antibodies, the engagement of which by antigen-antibody complexes controls their 
      responses. When aggregated on the plasma membrane, high-affinity immunoglobulin E 
      (IgE) receptors (FcepsilonRI) and low-affinity IgG receptors (FcgammaRIIIA in mice, FcgammaRIIA 
      in humans) induce these cells to release and secrete proinflammatory mediators, 
      chemokines, and cytokines that account for clinical symptoms. When coaggregated 
      with activating receptors on the same cells, other low-affinity IgG receptors 
      (FcgammaRIIB in both species) inhibit mast cell and basophil activation. We found 
      that FcgammaRIIB inhibited not only signals triggered by activating receptors with 
      which they were coengaged (cis-inhibition), but also signals triggered by 
      receptors engaged independently (trans-inhibition). Trans-inhibition acted upon 
      the FcepsilonRI-dependent activation of mouse mast cells, mouse basophils, and human 
      basophils, and upon growth factor receptor (Kit)-dependent normal mouse mast cell 
      proliferation, as well as the constitutive in vitro proliferation and the in vivo 
      growth of oncogene (v-Abl)-transformed mastocytoma cells. Trans-inhibition was 
      induced by receptors, whether inhibitory (FcgammaRIIB) or activating (FcepsilonRI), which 
      recruited the lipid phosphatase SHIP1. By hydrolyzing PI(3,4,5)P(3), SHIP1 
      induced a global unresponsiveness that affected biological responses triggered by 
      receptors that use phosphoinositide 3-kinase to signal. These data suggest that 
      trans-inhibition controls numerous physiological and pathological processes, and 
      that it may be used as a therapeutic tool in inflammation, especially but not 
      exclusively, in allergy and autoimmunity.
CI  - Copyright (c) 2016, American Association for the Advancement of Science.
FAU - Malbec, Odile
AU  - Malbec O
AD  - Institut Pasteur, Departement d'Immunologie, Unite d'Allergologie Moleculaire et 
      Cellulaire, Paris, France.
AD  - Inserm, Unite 760, Paris, France.
FAU - Cassard, Lydie
AU  - Cassard L
AD  - Institut Pasteur, Departement d'Immunologie, Unite d'Allergologie Moleculaire et 
      Cellulaire, Paris, France.
AD  - Inserm, Unite 760, Paris, France.
FAU - Albanesi, Marcello
AU  - Albanesi M
AD  - Institut Pasteur, Departement d'Immunologie, Unite d'Allergologie Moleculaire et 
      Cellulaire, Paris, France.
AD  - Inserm, Unite 760, Paris, France.
FAU - Jonsson, Friederike
AU  - Jonsson F
AD  - Institut Pasteur, Departement d'Immunologie, Unite d'Allergologie Moleculaire et 
      Cellulaire, Paris, France.
AD  - Inserm, Unite 760, Paris, France.
FAU - Mancardi, David
AU  - Mancardi D
AD  - Institut Pasteur, Departement d'Immunologie, Unite d'Allergologie Moleculaire et 
      Cellulaire, Paris, France.
AD  - Inserm, Unite 760, Paris, France.
FAU - Chicanne, Gaetan
AU  - Chicanne G
AD  - Inserm, Unite 1048, Toulouse, France.
AD  - Universite Toulouse 3, Toulouse, France.
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, Toulouse, France.
FAU - Payrastre, Bernard
AU  - Payrastre B
AD  - Inserm, Unite 1048, Toulouse, France.
AD  - Universite Toulouse 3, Toulouse, France.
AD  - Institut des Maladies Metaboliques et Cardiovasculaires, Toulouse, France.
FAU - Dubreuil, Patrice
AU  - Dubreuil P
AD  - Inserm, Unite 1068, Centre de Recherche en Cancerologie de Marseille, Marseille, 
      France.
AD  - Institut Paoli-Calmettes, Marseille, France.
AD  - Aix Marseille Universite, Marseille, France.
AD  - CNRS, UMR 7258, Marseille, France.
FAU - Vivier, Eric
AU  - Vivier E
AD  - Centre d'Immunologie de Marseille-Luminy, Aix Marseille Universite, Inserm, CNRS, 
      Marseille, France.
AD  - Hopital de la Conception, Marseille, France.
FAU - Daeron, Marc
AU  - Daeron M
AD  - Institut Pasteur, Departement d'Immunologie, Unite d'Allergologie Moleculaire et 
      Cellulaire, Paris, France. marc.daeron@pasteur.fr.
AD  - Inserm, Unite 760, Paris, France.
AD  - Centre d'Immunologie de Marseille-Luminy, Aix Marseille Universite, Inserm, CNRS, 
      Marseille, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161220
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (FCGR2A protein, human)
RN  - 0 (FCGR2B protein, human)
RN  - 0 (FcgammaRIIIA protein, mouse)
RN  - 0 (Fcgr2b protein, mouse)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Receptors, IgE)
RN  - 0 (Receptors, IgG)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.1.3.86 (INPP5D protein, human)
RN  - EC 3.1.3.86 (Inpp5d protein, mouse)
RN  - EC 3.1.3.86 (Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases)
SB  - IM
MH  - Animals
MH  - Basophils/*immunology
MH  - *Cell Proliferation
MH  - Humans
MH  - Mast Cells
MH  - Mice
MH  - Phosphatidylinositol 3-Kinases/genetics/immunology
MH  - Phosphatidylinositol Phosphates/genetics/immunology
MH  - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases/genetics/immunology
MH  - Receptors, IgE/*immunology
MH  - Receptors, IgG/genetics/*immunology
MH  - Signal Transduction/*immunology
EDAT- 2016/12/22 06:00
MHDA- 2017/11/29 06:00
CRDT- 2016/12/22 06:00
PHST- 2016/12/22 06:00 [entrez]
PHST- 2016/12/22 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
AID - 9/459/ra126 [pii]
AID - 10.1126/scisignal.aag1401 [doi]
PST - epublish
SO  - Sci Signal. 2016 Dec 20;9(459):ra126. doi: 10.1126/scisignal.aag1401.