MicroRNA-148a Facilitates Inflammatory Dendritic Cell Differentiation and Autoimmunity by Targeting MAFB

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2020 Mar 28

PMID 32213710

Citations 8

Authors

Yao Meng

Jun Li

Zhizhong Ye

Zhihua Yin

Qing Sun

Zhuojun Liao

Guanhua Li

Jun Deng

Lu Liu

Yuqing Yu

Li Wu

Haibo Zhou

Nan Shen

Affiliations

Soon will be listed here.

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.

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