MicroRNA-183/96/182 cluster regulates iNKT cell development and function (IRM7P.706)

Abstract

Abstract MicroRNAs (miRNAs), a class of non-coding small RNAs. Invariant Natural Killer T (iNKT) cells are potent regulators of diverse immune responses. Our previous study indicated that lack of miRNAs following the deletion of Dicer, a miRNAs-processing enzyme, affect iNKT cell development and function (PNAS, 2009). However, the roles of specific miRNA in iNKT cell development and function remain unclear. The miR-183/96/182 cluster, composed of 3 miRNA genes, is significantly upregulated upon T cell activation. In this study, we investigate the role of miR-183/96/182 cluster on development and function of iNKT cells, using miR-183/96/182 knockout (KO) mice. We found that the frequency of immature iNKT cells significantly increased, while mature iNKT cells significantly decreased in thymus of KO mice compared to littermate control (P<0.05), indicating the blockage of iNKT cell development in thymus. Furthermore, lack of miR-183/96/182 resulted in a substantial reduction of iNKT cell number (p<0.05) in the thymus and in spleen. The mutant iNKT cells displayed defective cytokine production, including IL-4 and IFNγ, compared to iNKT cells from littermate control (P<0.05). Finally, bone marrow chimera transferring experiments further suggested the miR-183/96/182 cluster controlled iNKT cell development and function by cell-intrinsic characteristics. Thus, our data define a specific role of miR-183/96/182 cluster in the development and function of iNKT cells.