1355 TRPV3 mediates cutibacterium acnes-induced chemotaxis and inflammation in sebocytes

TRPV3 mediates itch and inflammation in keratinocytes and plays an important role in atopic dermatitis, however, whether and how TRPV3 is involved in the pathogenesis of acne remains unclear. Thus, we explored the effects of TRPV3 on sebaceous glands (SGs) inflammation, its relation to cutibacterium acnes (C.acnes), and the underlying mechanisms in vitro and in vivo. Our study found that TRPV3 overexpression activated the Toll-like receptor 2 (TLR2)- Nuclear factor kappa-B (NF-κB) signal pathway and promoted the release of acne-related inflammatory cytokines and chemokines significantly (ranged from 1 to 7 fold, p<0.05), which contributed to the chemotaxis of neutrophils to SZ95 sebocytes and further amplified the inflammatory responses. Conversely, TRPV3 genetic deletion or pharmacological inhibition by its specific inhibitor both ameliorated the inflammatory phenotype in human SZ95 sebocytes and C.acnes-induced acne-like mouse model. Mechanistically, C.acnes could upregulate the expression of TRPV3, which further activates NF-κB signaling by regulating TLR2 and subsequently promote downstream inflammatory cytokines and chemokines releases. In conclusion, our study revealed a previously unreported association between TRPV3 and C.acnes, which is involved in the development of acne inflammation and may suggest TRPV3 as a novel therapeutic target for acne vulgaris and other disorders of the pilosebaceous unit.