968 A role for immunity to the microbiota in nerve overgrowth display in psoriasis skin

We aim to understand the role of immunity microbiota and IL17 in nerve overgrowth display psoriasis skin. used a model pre-exposure imiquimod (IMQ) induce skin inflammation mice. Skin sensory neurons participate physiology immunity. released by commensal-specific Th17 directly signals via IL17RA promotes regeneration upon injury. Neurogenic is essential psoriasis. Psoriasis patients report neuro-cutaneous symptoms such as neurogenic pain. Pre-exposure commensals (S. aureus, C. albicans) dramatically exacerbate through RNA-seq analysis CD4+, CCR6+, FoxP3- T cells, showed that commensals, upregulate genes involved interaction setting inflammation. Confocal imaging psoriatic mice dramatic increase fibers superficial layers Those overgrowing nerves closely interact with CD4 cells. Overgrowing are composed CGRP+ CGRP- fibers. Nerve endings shaped multibranched opposite linear observed control have been described highly pruritic disease: prurigo nodularis, which single-cell human skin, signature. IMQ-induced reduced IL17ra KO compared WT mice, suggesting central IL17A-IL17ra axis this process. Acute depletion Langerhans cell diphtheria toxin Langerin-DTR decreases while maintained, distinctive pathway between itch. Our work suggests Th17, langherans cells overspreading.