Microbial dysbiosis in the skin has been implicated in the pathogenesis of atopic dermatitis (AD); however, whether and how changes in the skin microbiome initiate skin inflammation, or vice versa, remains poorly understood. Here, we report that the levels of sebum and its microbial metabolite, propionate, were lower on the skin surface of AD patients compared with those of healthy individuals. Topical propionate application attenuated skin inflammation in mice with MC903-induced AD-like dermatitis by inhibiting IL-33 production in keratinocytes, an effect that was mediated through inhibition of HDAC and regulation of the AhR signaling pathway. Mice lacking sebum spontaneously developed AD-like dermatitis, which was improved by topical propionate application. A proof-of-concept clinical study further demonstrated the beneficial therapeutic effects of topical propionate application in AD patients. In summary, we have uncovered that the dysregulated sebum–microbial metabolite–IL-33 axis might play an initiating role in AD-related skin inflammation, thereby highlighting novel therapeutic strategies for the treatment of AD.

Fang X, et al. Ann Dermatol. 2022 Apr;34(2):139-143. https://doi.org/10.5021/ad.2022.34.2.139

The pilosebaceous units (PSUs) are essential micro‐organs for skin homeostasis, yet human vellus hair‐associated PSUs remain largely understudied. Here, we present a single‐nucleus transcriptomic atlas of PSUs from the back skin of healthy young and aged males, revealing extensive age‐associated cellular and transcriptional remodeling within this niche. We show that aging is accompanied by reduced relative representation of bulge hair follicle stem cells, together with altered regeneration‐associated transcriptional programs. Sebocytes display enhanced androgen responsiveness coupled with increased lipid biosynthetic activity during aging. Concurrently, an ion channel‐enriched follicular population shows increased representation with age and exhibits stress‐ and inflammation‐associated transcriptional features. In parallel, an innate immune‐like melanocyte subset shows reduced relative representation during aging, coinciding with changes in inferred melanocyte–immune communication. Notably, immune subsets in aged PSUs display coordinated changes in metabolic pathway signatures, suggesting an association between immune remodeling and metabolic state. Together, our findings highlight the aged PSU as a focal site where epithelial, immune, and metabolic alterations converge during skin aging. This work establishes a comprehensive single‐nucleus atlas of human vellus PSU aging and provides a framework for understanding how aging reshapes pilosebaceous niche biology, with potential implications for age‐associated cutaneous inflammation and dysfunction.