MicroRNA-148a facilitates inflammatory dendritic cell differentiation and autoimmunity by targeting MAFB
- 23 April 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
Abstract
Monocyte-derived DCs (moDCs) have been implicated in the pathogenesis of autoimmunity, but the molecular pathways determining the differentiation potential of these cells remain unclear. Here, we report that microRNA-148a (miR-148a) serves as a critical regulator for moDC differentiation. First, miR-148a deficiency impaired the moDC development in vitro and in vivo. A mechanism study showed that MAFB, a transcription factor that hampers moDC differentiation, was a direct target of miR-148a. In addition, a promoter study identified that miR-148a could be transcriptionally induced by PU.1, which is crucial for moDC generation. miR-148a ablation eliminated the inhibition of PU.1 on MAFB. Furthermore, we found that miR-148a increased in monocytes from patients with psoriasis, and miR-148a deficiency or intradermal injection of antagomir-148a immensely alleviated the development of psoriasis-like symptoms in a psoriasis-like mouse model. Therefore, these results identify a pivotal role for the PU.1-miR-148a-MAFB circuit in moDC differentiation and suggest a potential therapeutic avenue for autoimmunity.Funding Information
- Sanming Project of Medicine in Shenzhen (SZSM201602087)
- National Natural Science Foundation of China (31600706,31630021,81974252)
- Shenzhen Science and Technology Project (JCYJ20180504170414637)
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