The study shows that a skin‑applied compound called tapinarof, which turns on the aryl hydrocarbon receptor (AhR), can calm down the over‑active immune cells (mast cells) that are driven by the peptide LL‑37 in rosacea. It does this by boosting the cell’s recycling system (autophagy), which in turn lowers inflammation markers.

Activation of the aryl hydrocarbon receptor (AhR) ameliorates LL-37-induced rosacea-like dermatitis in mice, whereas mast cells and cytokine overexpression are prominent features in rosacea skin. To evaluate the potential mechanisms of AhR activation on autophagy and degranulation of mast cells in rosacea. LL-37 treated mast cells were used to mimic rosacea. An AhR agonist (tapinarof) was applied to LL-37 induced mast cells. Furthermore, an autophagy agonist (RAPA) and an inhibitor (CQ) was added to investigate the mechanisms of autophagy. Western blot and RT-qPCR assessed cell degranulation (Cma1, Tpsab1) and cytokines (MMP9, TNF-α, and IL-6). Changes in cell morphology were observed under a microscope. Autophagy markers (LC3 and p62) were examined using Western blot and cellular immunofluorescence. LL-37 upregulated the expressions of Cma1, Tpsab1, MMP9, TNF-α, and IL-6, which were then reduced by tapinarof treatment for 24 h. LC3B-I was converted to LC3B-II and p62 was reduced gradually with increasing concentration of tapinarof, indicating that autophagy was enhanced. RAPA enhanced the expression of LC3B-II on LL-37-induced mast cells, similar to tapinarof, while CQ partially inhibited the ability of tapinarof to induce autophagy in mast cells. Moreover, CQ reversed tapinarof's suppression of Cma1, Tpsab1, MMP9, TNF-α and IL-6 on LL-37 treated mast cells. The present study showed that activation of AhR ameliorated degranulation of LL-37-induced mast cells in rosacea through enhancing autophagy, offering a new option for rosacea treatment.