Natural cytotoxicity receptor splice variants orchestrate the distinct functions of human natural killer cell subtypes

• Published in: Nature communications 2015-12, Vol.6 (1), p.10183-10183, Article 10183
• Main Authors: Siewiera, Johan, Gouilly, Jordi, Hocine, Hocine-Rachid, Cartron, Géraldine, Levy, Claude, Al-Daccak, Reem, Jabrane-Ferrat, Nabila
• Format: Article
• Language: English
• Subjects: 13; 14; 14/19; 38; 38/77; 631/250/1619/382; 631/250/516; 96; 96/21; 96/31; Adolescent; Adult; Angiogenesis; Cells; Cytokines; Cytokines - genetics; Cytokines - metabolism; Cytotoxicity; Decidua - cytology; Female; Gene Expression Regulation - physiology; Humanities and Social Sciences; Humans; Immunology; Innate immunity; Killer Cells, Natural - classification; Killer Cells, Natural - physiology; Life Sciences; multidisciplinary; Physiology; Pregnancy; Protein Isoforms - genetics; Protein Isoforms - metabolism; Receptors, Natural Cytotoxicity Triggering - genetics; Receptors, Natural Cytotoxicity Triggering - metabolism; Science; Science (multidisciplinary); Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10183

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. Decidual natural killer (NK) cells from the pregnant uterus play an important role in the physiology of pregnancy and differ functionally from peripheral blood NK cells. Siewiera et al . reveal that this is partly due to the differential expression of splice variants of natural cytotoxicity receptors by these two cell subsets.