miR-146a downregulates epidermal Langerhans cell-mediated antigen presentation / 中华微生物学和免疫学杂志

ABSTRACT

Objective:To investigate the role of miR-146a in regulating the homeostasis and function of epidermal Langerhans cells (LCs).Methods:Fresh and in vitro cultured epidermal LCs were isolated and purified by flow cytometry (FCM). The expression of miR-146a in LCs was detected by quantitative PCR (qPCR). The percentages of epidermal LCs in wild-type (WT) and miR-146a conventional knockout (miR-146a cKO) mice were analyzed by FCM. The expression of major histocompatibility complex Ⅱ (MHCⅡ) and co-stimulatory molecules (CD86 and CD80) was analyzed by FCM to evaluate the effect of miR-146a on the maturation of LCs. The percentage of Dextran-FITC + LCs was detected by FCM to evaluate the effect of miR-146a on the phagocytic function of LCs. In vitro and in vivo experiments were used to analyze the ability of miR-146a-deficient and -sufficient LCs to stimulate the proliferation of CD8 + OT-ⅠT cells and CD4 + OT-Ⅱ T cells. Results:The expression of miR-146a was significantly increased in mature LCs than in the freshly isolated LCs. There was no significant difference in the number of epidermal LCs between wild-type (WT) and miR-146a cKO mice. After a 48 h culture in vitro, the expression of MHCⅡ, CD86 and CD80 in the epidermal LCs of miR-146a cKO mice was similar to that of WT mice. Moreover, miR-146a deletion had no significant influence on antigen uptake by LCs. However, miR-146a deficiency enhanced the antigen-presenting ability of LCs that could stimulate the proliferation of OVA-specific CD8 + OT-Ⅰ T cells and CD4 + OT-Ⅱ T cells. Conclusions:miR-146a had no influence on the homeostasis, maturation and phagocytosis of LCs, but enhanced the antigen-presenting function.