Related Experiment Video
Updated: Mar 28, 2026

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
Natural cytotoxicity receptor splice variants orchestrate the distinct functions of human natural killer cell
Johan Siewiera1,2,3, Jordi Gouilly1,2,3, Hocine-Rachid Hocine4
1INSERM UMR 1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.
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.
Insights
Natural killer (NK) cell receptors NKp46, NKp44, and NKp30 have splice variants with unknown roles. This study shows these variants differentiate distinct NK cell subsets, impacting pregnancy and immunity.
Area of Science:
- Immunology
- Cell Biology
- Reproductive Biology
Background:
- Natural cytotoxicity receptors (NCRs) like NKp46, NKp44, and NKp30 are crucial for natural killer (NK) cell function.
- NK cell genes transcribe into multiple splice variants, but their physiological significance remains largely unexplored.
Purpose of the Study:
- To investigate the differential expression and functional relevance of NKp30 and NKp44 splice variants in distinct human NK cell subsets.
- To determine if the decidual microenvironment influences NK cell splice variant profiles and function.
Main Methods:
- Comparative analysis of NKp30/NCR3 and NKp44/NCR2 splice variant expression in decidual NK (dNK) cells and peripheral blood NK (pNK) cells.
- In vitro experiments exposing pNK cells to decidual cytokines to assess changes in splice variant profiles and cellular functions.
Main Results:
- Decidual NK (dNK) cells and peripheral blood NK (pNK) cells exhibit distinct expression patterns of NKp30/NCR3 and NKp44/NCR2 splice variants.
- Exposure to decidual microenvironment-enriched cytokines induced a shift in pNK cell splice variant profiles towards the dNK cell phenotype.
- This phenotypic switch in pNK cells correlated with reduced cytotoxic activity and significant alterations in their secretome, characteristic of the decidual NK cell phenotype.
Conclusions:
- NKp30/NCR3 and NKp44/NCR2 splice variants serve as key markers for functionally distinct NK cell subsets.
- The decidual microenvironment actively shapes NK cell function through modulation of NCR splice variants, highlighting their physiological importance in pregnancy.
- This study provides the first conclusive evidence for the physiological relevance of natural cytotoxicity receptor splice variants in immune regulation.
More Related Videos
Related Concept Videos
Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
RNA Splicing
Diversity of Antigen Receptors
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Alternative RNA Splicing
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...

