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- W13642012 abstract "Abstract CEACAM1 (CD66a) is involved in many biological processes, including regulation of lymphocyte activation. Although granulocytes highly express CEACAM1, the role of CEACAM1 in granulopoiesis and granulocyte dependent immune responses is not well understood. We showed here that CEACAM1 expression correlated with granulocytic differentiation and CEACAM1-/- mice developed severe neutrophilia in a cell-autonomous fashion associated with hyper-proliferation of granulocyte progenitors. Also, the regulation of CEACAM1 on progenitor cells was granulocytic lineage specific. We found CEACAM1 acted as a co-inhibitory receptor for G-CSFR, leading to the down-regulation of Stat3 activity. This inhibitory effect was dependent on G-CSF induced phosphorylation of ITIMs on CEACAM1 and the recruitment of SHP-1. Moreover, CEACAM1-/- mice were hypersensitive to Listeria monocytogenes (LM) infection with accelerated mortality due to augmented neutrophil liver infiltration and enhanced cytokine levels. Reintroduction of CEACAM1 restored normal granulopoiesis and host sensitivity to LM infection upon transduction into CEACAM1-/- mice; Mutation of the Tyr residues in its ITIMs abrogated this restoration. Finally, knocking down Stat3 in CEACAM1-/- mice rescued normal granulopoiesis and attenuated host sensitivity to LM infection. Thus, we identified CEACAM1 as a co-inhibitory receptor for G-CSFR regulating granulopoiesis and affecting the host innate immune response to bacterial infections." @default.
- W13642012 created "2016-06-24" @default.
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- W13642012 date "2010-04-01" @default.
- W13642012 modified "2023-09-23" @default.
- W13642012 title "CEACAM1 regulates granulopoiesis through inhibition of G-CSFR-Stat3 signaling in an ITIM-SHP-1 dependent manner (36.20)" @default.
- W13642012 doi "https://doi.org/10.4049/jimmunol.184.supp.36.20" @default.
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