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.

Background Dupilumab is an antibody against interleukin 4 receptor α, used in treating atopic dermatitis (AD). Objectives To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate-to-severe AD. Methods In this randomized, double-blind, placebo-controlled, parallel-group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both Investigator’s Global Assessment (IGA) score of 0–1 and a reduction from baseline of ≥2 points at week 16. Results Overall, 165 patients (mean age: 30.6 years; 71.5% male) were randomized: 82 to dupilumab and 83 to placebo. At week 16, 26.8% of patients in the dupilumab group and 4.8% of patients in the placebo group achieved the primary endpoint (difference, 22.0%; 95% confidence interval [CI], 11.37–32.65%; p<0.0001). Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥75% reduction in the Eczema Area and Severity Index score (57.3% vs 14.5%; difference, 42.9%; 95% CI, 29.75–55.97%; p<0.0001) and had ≥3-point (52.4% vs 9.6%; difference, 42.8%; 95% CI, 30.26–55.34%; p<0.0001) and ≥4-point (39.0% vs 4.8%; difference, 34.2%; 95% CI, 22.69–45.72%; p<0.0001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of TEAEs during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis, and injection site reaction was higher in the dupilumab group than in the placebo group. Conclusions In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favorable safety profile.