New miRNA Signature Heralds Human NK Cell Subsets at Different Maturation Steps: Involvement of miR-146a-5p in the Regulation of KIR Expression

Frontiers in Immunology

Emanuela Marcenaro¹  Simona Sivori¹  Alessandro Moretta¹  Marco Greppi¹  Simona Candiani²  Silvia Pesce³  Lorenzo Moretta⁴  Margherita Squillario⁵  Annalisa Barla⁵  Patrizio Castagnola⁶  Fabrizio Loiacono⁷ 

[1] Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy;Department of Earth Science, Environment and Life (DISTAV), University of Genoa, Genoa, Italy;Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy;Department of Immunology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy;Department of Informatic Bioengeneering, Robotic and System Engeneering, University of Genoa, Genoa, Italy;Department of Integrated Oncological Therapies, IRCCS San Martino Polyclinical Hospital, Genoa, Italy;Immunology Operative Unit, IRCCS San Martino Polyclinical Hospital, Genoa, Italy;

关键词: NK cells;    miRNA;    KIR;    CD56bright;    CD56dim;    NK cell subsets;   

DOI  :  10.3389/fimmu.2018.02360

来源: DOAJ

【 摘 要 】

Natural killer cells are cytotoxic innate lymphoid cells that play an important role for early host defenses against infectious pathogens and surveillance against tumor. In humans, NK cells may be divided in various subsets on the basis of the relative CD56 expression and of the low-affinity FcγRIIIA CD16. In particular, the two main NK cell subsets are represented by the CD56bright/CD16−/dim and the CD56dim/CD16bright NK cells. Experimental evidences indicate that CD56bright and CD56dim NK cells represent different maturative stages of the NK cell developmental pathway. We identified multiple miRNAs differentially expressed in CD56bright/CD16− and CD56dim/CD16bright NK cells using both univariate and multivariate analyses. Among these, we found a few miRNAs with a consistent differential expression in the two NK cell subsets, and with an intermediate expression in the CD56bright/CD16dim NK cell subset, representing a transitional step of maturation of NK cells. These analyses allowed us to establish the existence of a miRNA signature able to efficiently discriminate the two main NK cell subsets regardless of their surface phenotype. In addition, by analyzing the putative targets of representative miRNAs we show that hsa-miR-146a-5p, may be involved in the regulation of killer Ig-like receptor (KIR) expression. These results contribute to a better understanding of the physiologic significance of miRNAs in the regulation of the development/function of human NK cells. Moreover, our results suggest that hsa-miR-146a-5p targeting, resulting in KIR down-regulation, may be exploited to generate/increment the effect of NK KIR-mismatching against HLA-class I+ tumor cells and thus improve the NK-mediated anti-tumor activity.

【 授权许可】

Unknown