Research ArticleImmunology

Trans-inhibition of activation and proliferation signals by Fc receptors in mast cells and basophils

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Science Signaling  20 Dec 2016:
Vol. 9, Issue 459, pp. ra126
DOI: 10.1126/scisignal.aag1401

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Allergic inflammation gets “SHIP”ped out

Fc receptors bind to the Fc portion of antibodies. Fcγ receptors (FcγR) bind to IgG, whereas Fcε receptors (FcεRI) bind to IgE antibodies. Antigen recognition by FcεRI-bound IgE on mast cells and basophils triggers receptor clustering and the release of inflammatory mediators responsible for allergic symptoms. Coclustering of FceRI with FcγRIIB inhibits activation signals (cis-inhibition) by recruiting SHIP1. Malbec et al. showed that FcγRIIB also inhibited signaling through receptors with which these receptors were not coclustered, indicating that FcγRIIB can also mediate trans-inhibition. FcγRIIB limited PIP3-dependent signaling by not only the receptors involved in allergic responses, but also growth factor receptors. FcγRIIB also reduced the oncogen-induced proliferation of mastocytoma cells. These data suggest that manipulating trans-inhibition may provide a general therapy to inhibit inflammatory signaling.

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