Trans-inhibition : a new inhibitory by property of FCgammaRIIB
type: Distribution
access URL: https://theses.hal.science/tel-00833016
format: HTML
issued: 2026-05-10T18:29:24.188577
modified: 2026-05-10T18:29:24.174233

Trans-inhibition : a new inhibitory by property of FCgammaRIIB
type: Dataset
contact point: Organization
  fn: CCSD
keyword: inhibition
keyword: theses
keyword: rfc
keyword: sdvimmlife-sciences-q-bioimmunology
keyword: infoeu-reposemanticsdoctoralthesis
keyword: allergie
keyword: itim
keyword: ship1
keyword: mastocytes
landing page: https://theses.hal.science/tel-00833016
description: Like other Immunoreceptor Tyrosine-based Activation Motif (ITAM)-containing receptors, high-affinity IgE receptors (FcγRI), which initiate allergic reactions, generate activation signals when engaged on mast cells and basophils. By contrast, low-affinity receptors for IgG, FcγRIIB contain an Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) generating inhibitory signals when co-aggregated with ITAM-bearing receptors. They can also inhibit mast cell proliferation induced by Tyrosine Kinase Receptors such as Kit. Inhibitory capabilities of FcγRIIB depend on the recruitment of the SH2 domain-containing Inositol 5-Phosphatase SHIP1, which in turn decreases the amount of the secondary messenger Phosphatidyl Inositol trisphosphate PI(3,4,5)P3. The aim of my thesis was to investigate whether the coligation of an activating receptor with FcγRIIB could inhibit cell activation induced by other receptors that were not co-engaged with FcγRIIB. I could show that, indeed, FcγRIIB when co-aggregated with FcγRI, inhibited not only activation signals induced by co-aggregated FcγRI (cis-inhibition), but also by independently engaged FcγRI or by Kit (trans-inhibition). Vice versa, the co-aggregation of Kit with FcγRIIB inhibited mast cell activation induced by FcγRI. Trans-inhibition was not limited to mast cells but was also effective in mouse and human basophils. Finally, the co-aggregation of Kit and FcγRIIB inhibited the oncogen Abl-dependent proliferation of a mouse mastocytoma. In conclusion, trans-inhibition is a novel SHIP1-dependent regulatory mechanism that can generate an anergic state, preventing cells from responding to various activation and proliferation signals
identifier: NNT: 2012PAO66247
issued: 2026-05-10T18:29:24.186618
language: fr
modified: 2026-05-10T18:29:24.186622

test_moissonnage_selune
type: Agent