miRNomes of haematopoietic stem cells and dendritic cells identify miR-30b as a regulator of Notch1

Su, Xiaoping; Qian, Cheng; Zhang, Qian; Hou, Jin; Gu, Yan; Han, Yanmei; Chen, Yongjian; Jiang, Minghong; Cao, Xuetao

In the immune system, Notch signaling, as a highly conserved pathway, has been implicated in determining cell fate including cell growth, differentiation and survival. Recently, the role of Notch signaling has been found to be important in the function of antigen-presenting cells 45 . Our work showed that Notch1 and downstream signaling, targeted by the enriched miR-30b expression in DCreg, negatively regulated the preferential IL-10 and NO production in DCreg, which is consistent with the recent report that Notch1 signaling could inhibit IL-10 production in macrophages stimulated with TLR agonists 46 . More recently, we demonstrated that Notch signaling suppressed TLR-triggered inflammatory cytokine production by inhibiting ERK1/2mediated NF-kB activity in macrophages 47 . We previously found that upregulated IL-10 production might be due to enhanced activation of ERK1/2 in DCreg 48 . Our findings suggest that miR-30b can target Notch1 to retain the negative regulatory role of DCreg through enhanced activation of ERK1/2. In contrast, previous reports presented that Notch signaling was required for IL-10 production in T cells 49 . These discrepancies may be due to the distinct roles of Notch1 signaling in the different cell types, which may include the different epigenetic modification in the promoters of IL-10 and NO or the different activation of multiple transcription factors to the binding sites of IL-10 and NO promoter regions, thus suggesting distinct regulatory mechanisms in different cell types.