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

Johan Siewiera, Jordi Gouilly, Hocine-Rachid Hocine, Géraldine Cartron, Claude Levy, Reem Al-Daccak and Nabila Jabrane-Ferrat ()
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Johan Siewiera: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP)
Jordi Gouilly: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP)
Hocine-Rachid Hocine: INSERM UMRS976 and Université Paris-Diderot, Hôpital Saint Louis
Géraldine Cartron: Service de Gynécologie-Obstétrique, Centre Hospitalo-Universitaire de Toulouse, Hôpital Paule de Viguier
Claude Levy: Service de Gynécologie-Obstétrique Clinique Sarrus-Teinturiers
Reem Al-Daccak: INSERM UMRS976 and Université Paris-Diderot, Hôpital Saint Louis
Nabila Jabrane-Ferrat: INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP)

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms10183

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