title: CD300c is uniquely expressed on CD56 bright Natural Killer Cells and differs from CD300a upon ligand recognition.
abstract: Paired receptors on NK cells recognize similar ligands with varied strength of binding ability and perform different functions. The CD300 molecules are emerging as novel immune regulators in health and disease due to their interaction with their lipid-nature ligands. Particularly, the paired receptors CD300c and CD300a have been shown to elicit activating and inhibitory capabilities, respectively. In the current study, we seek to investigate the expression and function of CD300c on human NK cells. We demonstrate that IL-2 and IL-15 treatment significantly induce CD300c expression exclusively on CD56(bright) NK cells. CD300c up-regulation requires STAT5 and its expression is inhibited by IL-4. Consistently, IL-2 secreted from activated CD4(+) T cells specifically induces the expression of CD300c on CD56(bright) NK cells. Crosslinking CD300c with a specific antibody enhances the proficiency of CD56(bright) NK cells to degranulate and induce chemokine and cytokine secretion. We also show the differential binding of CD300a and CD300c to their ligands phosphatidylethanolamine (PE) and phosphatidylserine (PS) and their differential ability to affect CD56(bright) NK cell functions. Our results provide an insight into the novel set of paired receptors CD300a and CD300c that are distinctively expressed on CD56(bright) NK cells with varied effector functions.
authors.affiliation: Division of Biotechnology Review and Research-I, Office of Biotechnology Products Review and Research, CDER, Food and Drug Administration, USA.
authors.forename: Milena
authors.initials: M
authors.lastname: Dimitrova
authors.affiliation: Immunopathology Group, BioCruces Health Research Institute, Barakaldo, Spain.|Immunotherapy Group, Basque Center for Transfusion and Human Tissues, Galdakao, Spain.
authors.forename: Olatz
authors.initials: O
authors.lastname: Zenarruzabeitia
authors.affiliation: Immunopathology Group, BioCruces Health Research Institute, Barakaldo, Spain.|Immunotherapy Group, Basque Center for Transfusion and Human Tissues, Galdakao, Spain.|Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Borrego
authors.affiliation: Division of Biotechnology Review and Research-I, Office of Biotechnology Products Review and Research, CDER, Food and Drug Administration, USA.
authors.forename: Venkateswara R
authors.initials: VR
authors.lastname: Simhadri
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019002:CD56 Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C515070:CD300A protein, human; C444139:CD300C protein, human; D019002:CD56 Antigen; D019409:Interleukin-15; D007376:Interleukin-2; D008024:Ligands; D008562:Membrane Glycoproteins; C522918:NCAM1 protein, human; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D011971:Receptors, Immunologic; D050799:STAT5 Transcription Factor; C483858:phosphatidylethanolamine