title: Natural cytotoxicity receptor splice variants orchestrate the distinct functions of human natural killer cell subtypes.
abstract: The natural cytotoxicity receptors NKp46/NCR1, NKp44/NCR2 and NKp30/NCR3 are critical for natural killer (NK) cell functions. Their genes are transcribed into several splice variants whose physiological relevance is not yet fully understood. Here we report that decidua basalis NK (dNK) cells of the pregnant uterine mucosa and peripheral blood NK (pNK) cells, two functionally distinct subsets of the physiological NK cell pool, display differential expression of NKp30/NCR3 and NKp44/NCR2 splice variants. The presence of cytokines that are enriched within the decidual microenvironment is sufficient to convert the splice variant profile of pNK cells into one similar to that of dNK cells. This switch is associated with decreased cytotoxic function and major adaptations to the secretome, hallmarks of the decidual phenotype. Thus, NKp30/NCR3 and NKp44/NCR2 splice variants delineate functionally distinct NK cell subsets. To our knowledge, this is the first conclusive evidence underlining the physiological importance of NCR splice variants.
authors.affiliation: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.|CNRS UMR 5282, Toulouse F-31300, France.|Université Toulouse III Paul Sabatier, CHU Purpan BP 3028, Toulouse F-31300, France.
authors.forename: Johan
authors.initials: J
authors.lastname: Siewiera
authors.affiliation: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.|CNRS UMR 5282, Toulouse F-31300, France.|Université Toulouse III Paul Sabatier, CHU Purpan BP 3028, Toulouse F-31300, France.
authors.forename: Jordi
authors.initials: J
authors.lastname: Gouilly
authors.affiliation: INSERM UMRS976 and Université Paris-Diderot, Hôpital Saint Louis, Paris 75010, France.
authors.forename: Hocine-Rachid
authors.initials: HR
authors.lastname: Hocine
authors.affiliation: Service de Gynécologie-Obstétrique, Centre Hospitalo-Universitaire de Toulouse, Hôpital Paule de Viguier, Toulouse 31059, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Cartron
authors.affiliation: Service de Gynécologie-Obstétrique Clinique Sarrus-Teinturiers, Toulouse 31300, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Levy
authors.affiliation: INSERM UMRS976 and Université Paris-Diderot, Hôpital Saint Louis, Paris 75010, France.
authors.forename: Reem
authors.initials: R
authors.lastname: Al-Daccak
authors.affiliation: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.|CNRS UMR 5282, Toulouse F-31300, France.|Université Toulouse III Paul Sabatier, CHU Purpan BP 3028, Toulouse F-31300, France.
authors.forename: Nabila
authors.initials: N
authors.lastname: Jabrane-Ferrat
mesh_terms: D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003656:Decidua / Q000166:cytology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000145:classification* / Q000502:physiology; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D055636:Receptors, Natural Cytotoxicity Triggering / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; D020033:Protein Isoforms; D055636:Receptors, Natural Cytotoxicity Triggering