Carcinoembryonic Antigen-Related Cell Adhesion Molecule-1 Regulates Granulopoiesis by Inhibition of Granulocyte Colony-Stimulating Factor Receptor

Although carcinoembryonic antigen-related cell adhesion moclecule-1 (CEACAM1) is an activation marker for neutrophils and delays neutrophil apoptosis, the role of CEACAM1 in granulopoiesis and neutrophil-dependent host immune responses has not been investigated CEACAM1 expression correlated with granulocytic differentiation, and Ceacam1(-/-) mice developed neutrophilia because of loss of the Src-homology-phosphatase-1 (SHP-1)-dependent inhibition of granulocyte colony-stimulating factor receptor (G-CSFR) signal transducer and activator of transcription (Stat3) pathway provided by CEACAM1 Moreover, Ceacam1(-/-) mice were hypersensitive to Listeria Monocyto genes (LM) infection with an accelerated mortality Reintroduction of CEACAM1 into Ceacam1(-/-) bone marrow restored normal granulopoiesis and host sensitivity to LM infection, while mutation of its immunoreceptor tyrosine-based inhibitory motifs (ITIMs) abrogated this restoration shRNA-mediated reduction of Stat3 amounts rescued normal granulopoiesis, attenuating host sensitivity to LM infection in Ceacam1(-/-) mice Thus, CEACAM1 acted as a coinhibitory receptor for G-CSFR regulating granuloporesis and host innate immune response to bacterial infections