MicroRNA155 Regulates Dendritic Cell Maturation Through Targeting MafB

MicroRNA155 (miR155) is involved in a range of physiological and pathological processes such as tumor development and progression, cardiovascular diseases, immune cell differentiation and development etc. Research on miR155 knockout mice shows that miR155 can promote the differentiation and proliferation of inflammatory cells including T17, Thl, macrophages etc, which results in inflammation and autoimmune diseases. Recent studies suggest that miR155 promotes dendritic cell differentiation and maturation through targeting TAB2 and c-Fos, and induces T cell proliferation and activation. These results indicate that the abnormal T cell proliferation found in miR155 defect mice may be due to inducing status of dendritic cells. However, the molecular mechanisms of miR155 during dendritic cell differentiation and maturation are not totally understood up to now.In our previous work, through the analysis of mRNA expression and microRNA expression profiling in human monocytes-derived dendritic cells, we found that the expression of miR155 was closely corelated to MafB. The bioinformatic prediction also suggested that MafB might be a target gene of miR155. Previous research has shown that MafB played an important role in the differentiation of myeloid progenitor cells to the macrophages or dendritic cells. Study in burn patients also showed that the increasing MafB level increased macrophages and leaded to the defect of dendritic cells. Together, these studies above strongly suggest that miR155 and MafB may play a decisive role in the directional differentiation and development from hematopoietic progenitor cells to dendritic cells and macrophages.In our study, using miR155 gene knockout mice bone marrow derived dendritic cells and DC2.4 cells, we found that the expression of miR155 and MafB was reversely correlated during dendritic cell maturation induced by LPS. Overexpression of miR155 mimics and luciferase reporter showed that MafB was a target of miR155. In addition, knockdown of MafB in dendritic cell enhanced the expression of co-receptors including CD40, CD80, CD83, CD86 and MHCII. This study discovered a new target of miR155, MafB, and indicated that miR155 might be involved in the regulation of dendritic cell maturation through MafB.