MiRNAs are required for the epidermal Langerhans cell development (36.18)

Abstract

Abstract Langerhans cells (LCs) are skin-resident DCs that express the C-type lectin Langerin and have a life cycle distinct from many other types of DCs. Even though LCs were first described more than 100 years ago, their development and immunological functions still remain enigmatic. MicroRNAs (miRNAs), a class of 21-25 nt single-stranded non-coding small RNAs, are increasingly being recognized as important regulators of gene expression through the inhibition of effective mRNA translation. Using Cre-loxP tissue-specific Dicer deletion, our laboratory and others have reported that deletion of miRNAs significantly affects the development and function of B, T, and NKT cells. To test the roles of miRNAs in the development of LCs, we generated a mouse strain with tissue-specific disruption of Dicer in the late stage of LC development mediated by Langerin-Cre. We found that Dicerfl/fl.langerinCre+ mice had significantly reduced number of epidermal LCs and the expression of Langerin was significantly reduced in miRNA-deficient I-Ab positive LCs. miRNA-deficient LCs have a defect on their maturation in vitro, but have normal capacity for antigen uptaking. Using BRDU staining, we found that increased both LC proliferation and apoptosis appear in Dicerfl/fl.langerinCre+ mice compared to WT mice. Thus, our findings highly suggest that miRNAs are required for the LC development and homeostasis.