Defensins mediate skin inflammation and itch in psoriasis.

Psoriasis is an inflammatory skin condition that features marked upregulation of keratinocyte-derived antimicrobial peptides, particularly β-defensins. Yet, the functions of these peptides in skin inflammation remain unclear. In this study, we used a defensin cluster-knockout mouse to evaluate the potential roles of defensins as neuroimmune modulators in psoriasis. Deletion of the defensin gene cluster (Def conditional knockout) in keratinocytes significantly attenuated imiquimod-induced psoriatic inflammation, with reduced hyperkeratosis, erythema, scaling, and expression of inflammatory cytokines and chemokines. In addition, the Def conditional-knockout mice exhibited reduced neutrophil and IL-17+ TCRγδ T-cell infiltration in the psoriatic skin, indicating a critical role of defensins in amplifying T helper 17 immunity. Behavioral analysis further revealed that the loss of defensins reduced psoriatic itch, and we showed that human β-defensin 2 directly activated small-diameter Mrgpra3 neurons to elicit robust scratching. Overall, our study revealed that β-defensins play an important role in mediating inflammation and itch associated with psoriasis by activating neutrophils, type 17 immune response, and pruriceptive sensory neurons, suggesting defensin signaling as a potential therapeutic target in psoriasis.

Abstract from PubMed