Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation

Article

关键词: DELTA T-CELLS;    PERIPHERAL LYMPHOID ORGANS;    DENDRITIC CELLS;    PLAQUE-FORMATION;    NERVOUS-SYSTEM;    RECEPTOR;    MICE;    IDENTIFICATION;    MONOCYTES;    CYTOKINE;   

DOI  :  10.1038/nature13199

来源: SCIE

【 摘 要 】

The skin has a dual function as a barrier and a sensory interface between the body and the environment. To protect against invading pathogens, the skin harbours specialized immune cells, including dermal dendritic cells (DDCs) and interleukin (IL)-17-producing gamma delta T (gamma delta T17) cells, the aberrant activation of which by IL-23 can provoke psoriasis-like inflammation(1-4). The skin is also innervated by a meshwork of peripheral nerves consisting of relatively sparse autonomic and abundant sensory fibres. Interactions between the autonomic nervous system and immune cells in lymphoid organs are known to contribute to systemic immunity, but how peripheral nerves regulate cutaneous immune responses remains unclear(5,6). We exposed the skin of mice to imiquimod, which induces IL-23-dependent psoriasis-like inflammation(7,8). Hereweshowthat a subset of sensory neurons expressing the ion channels TRPV1 and Na(v)1.8 is essential to drive this inflammatory response. Imaging of intact skin revealed that a large fraction of DDCs, the principal source of IL-23, is in close contact with these nociceptors. Upon selective pharmacological or genetic ablation of nociceptors(9-11), DDCs failed to produce IL-23 in imiquimod-exposed skin. Consequently, the local production of IL-23-dependent inflammatory cytokines by dermal gamma delta T17 cells and the subsequent recruitment of inflammatory cells to the skin were markedly reduced. Intradermal injection of IL-23 bypassed the requirement for nociceptor communicationwithDDCs and restored the inflammatory response(12). These findings indicate that TRPV1(+)Na(v)1.8(+) nociceptors, by interacting with DDCs, regulate the IL-23/IL-17 pathway andcontrol cutaneousimmune responses.

【 授权许可】

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