Updates on the Role of Innate Immunity’s Pattern Recognition Receptors in Vitiligo Pathogenesis and Therapeutic Potential

Jindi Feng, Lu Lu, Huimin He, Yubin Peng, Shiyu Zhang, Lu Yang, Yuehua Liu, Tao Wang Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, People’s Republic of ChinaCorrespondence: Yuehua Liu; Tao Wang, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China, Tel +86-10-69151543, Fax +86-10-69151502, Email [email protected]; [email protected]: Vitiligo is a complex, multifactorial disorder characterized by acquired skin pigment loss that strongly influences the physical and mental well-being of patients with vitiligo. The precise pathogenesis remains incompletely elucidated, but recent studies emphasize the significant roles of both innate and adaptive immunity. Pattern recognition receptors (PRRs), essential for innate immune sensing, significantly contribute to melanocyte destruction in vitiligo. In vitiligo patients, melanocytes and keratinocytes secrete substances like heat shock protein 70 (HSP70), high-mobility group box 1 protein (HMGB1), calreticulin (CRT), and S100 calcium-binding protein B (S100B) due to various internal and external influences. PRRs are capable of recognizing these “danger signals”. This recognition activates the immune response by stimulating innate immune cells, like plasmacytoid dendritic cells (pDCs) and natural killer cells (NK cells). The activation of innate immune cells leads to the release of cytokines and the presentation of melanocyte antigens to T cells, triggering the adaptive immune response. Activated CD8+ T cells release cytotoxic substances such as perforin and granzyme, which directly target and kill melanocytes. Cytokines like IFN-γ can concurrently stimulate keratinocytes to produce chemokines such as CXCL9 and CXCL10, which further recruit additional T cells, establishing an inflammatory amplification loop. This loop leads to continuous damage of melanocytes and ultimately results in the development of vitiligo. PRR inhibitors target the initial phase of the immune response cascade in vitiligo, offering a more fundamental and precise therapeutic approach with potential advantages in controlling disease activity and preventing recurrence. This review provides an overview of current research regarding PRRs and their ligands in vitiligo pathogenesis, with a focus on potential therapeutic strategies.Keywords: vitiligo, pattern recognition receptors, innate immunity, pathogenesis, damage-associated molecular patterns, pathogen-associated molecular patterns