Cutibacterium acnes extracellular vesicles: A new therapeutic target in acne modulated by myrtacine and celastrol

Summary: Abstract Body: Introduction: Acne is a chronic inflammatory skin condition involving the sebaceous glands, keratinocytes, skin microbiome, and innate immunity. Cutibacterium acnes (C. acnes), a skin bacterium, is classified into six phylotypes. Phylotype IA1 overgrowth is associated with acne lesions. C. acnes secretes Extracellular Vesicles (EVs) that contribute to skin inflammation. Objectives: This study aimed to assess the effects of Myrtacine® and Celastrol, alone or in combination, on cutaneous innate immunity using human skin models exposed to C. acnes EVs. Materials & Methods: EVs were isolated from two different strains of C. acnes phylotype IA1: T5 (healthy human skin) and A47 (inflammatory acne lesion). These EVs were applied to human keratinocytes (HaCaT cell line) and skin explants. Preventive treatment indicated addition of Myrtacine and Celastrol, alone or combined, to the cells or explants before EV incubation. In curative treatment, the skin models were exposed to EVs before addition of active ingredients. Subsequently, qPCR, ELISA, and immunohistochemistry were performed for select immune markers. Results: A47 EVs, but not T5 EVs, significantly increased proinflammatory and antimicrobial markers at transcript and protein levels. Myrtacine or Celastrol treatment, both preventive and curative, significantly reduced most markers. However, their combination further enhanced the inhibition of the immune response induced by EVs. Conclusion: Preventive and curative treatments with Myrtacine and Celastrol, alone or in combination, significantly decrease immune marker expression, suggesting their potential anti-inflammatory properties for acne therapy. Caroline T. Cheung¹, Céline Mias⁵, Ugo Lancien³, Stéphane Corvec⁴, Audrey Houcine⁵, Valérie Mengeaud², Amir Khammari^{1, 6}, Hélène Duplan⁵, Brigitte Dréno¹ 1. INCIT/IRS2/INSERM/UMR1302, Nantes Universite, Nantes, Pays de la Loire, France. 2. Medical Department, Laboratoires Dermatologiques Ducray SAS, Lavaur, France. 3. CHU Nantes Plastic Surgery, Nantes Universite, Nantes, Pays de la Loire, France. 4. CHU Nantes Bacteriology, Nantes Universite, Nantes, Pays de la Loire, France. 5. R&D department, Pierre Fabre Dermo-Cosmetique SAS, TOULOUSE, Occitanie, France. 6. CHU Nantes Dermatology, Nantes Universite, Nantes, Pays de la Loire, France. Innate Immunity, Microbiology, and Microbiome