Macrophage autophagy deficiency-induced CEBPB accumulation alleviates atopic dermatitis via impairing M2 polarization

作者：Yongcheng Zhu, Yunyao Liu, Yuxiang Ma, Liu Chen, He Huang, Siting Huang, Huiling Zhang, Yu‐Ying He, Yu‐Ying He, Cheng Tan, Yuan He, Yuan He, Lei Qiang · 发表于：Cell Reports · 年份：2023 · DOI：10.1016/j.celrep.2023.113430 · 被引用次数：43 · 研究领域：Dermatology and Skin Diseases、Immune Cell Function and Interaction、Inflammasome and immune disorders

Macroautophagy/autophagy plays a pivotal role in immune regulation. Its significance is evident in modulation of immune cell differentiation and maturation, physiologically and pathologically. Here, we investigate the role of macrophage autophagy on the development of atopic dermatitis (AD). By employing an MC903-induced AD mice model, we observe reduced cutaneous inflammation in macrophage Atg5 cKO mice compared with WT mice. Notably, there is a decreased infiltration of M2 macrophages in lesional skin from Atg5 cKO mice. Furthermore, impaired STAT6 phosphorylation and diminished expression of M2 markers are detected in autophagy-deficient macrophages. Our mechanistic exploration reveals that CEBPB drives the transcription of SOCS1/3 and SQSTM1/p62-mediated autophagy degrades CEBPB normally. Autophagy deficiency leads to CEBPB accumulation, and further promotes the expression of SOCS1/3. This process inhibits JAK1-STAT6 pathway activation and M2 marker expression. Together, our study indicates that autophagy is required for M2 activation and macrophage autophagy may be a promising target for AD intervention.