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

Macroautophagy/autophagy plays a pivotal role in immune regulation. Its significance is evident in modula-tion 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 in-hibits JAK1-STAT6 pathway activation and M2 marker expression. Together, our study indicates that auto-phagy is required for M2 activation and macrophage autophagy may be a promising target for AD intervention.

Automated summary

Macroautophagy has a significant role in the development of atopic dermatitis (AD), regulating inflammation and macrophage phenotype transition.