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Nociceptors: Not Just for Sensing

Summary and Comment |
May 13, 2014

Nociceptors: Not Just for Sensing

  1. Kenneth Y. Tsai, MD, PhD

Localized inflammation can be driven by a neural response that likely also causes sensations such as itch and pain.

  1. Kenneth Y. Tsai, MD, PhD

Repeated application of imiquimod produces inflammatory psoriasiform skin lesions in mice. Interleukin (IL)-23-mediated secretion of interleukins IL17 and IL22 prompts recruitment of inflammatory leukocytes and produces psoriasiform acanthosis. In human psoriatic skin, local anesthesia and denervation that reduce pain and itch also ameliorate the inflammatory response.

Riol-Blanco and colleagues investigated how peripheral nerves affect cutaneous immune responses — particularly, whether certain sensory neurons are essential to inflammatory response. Surprisingly, they found that ablation of TRPV1-expressing nociceptive neurons decreased imiquimod-related inflammation, acanthosis, and cytokine elaboration. This effect persisted even in mice lacking lymph nodes, and because lymphocyte extravasation was unaffected, they concluded that the effect is local.

They then identified a local population of dermal γδT cells that respond to IL23 by elaborating IL22F and IL17. In mice with ablated TRPV1 neurons, these T cells did not express IL22F and IL17 in response to imiquimod. Direct injection of IL23 generated an inflammatory response regardless of whether nociceptors were functional. Finally, the researchers identified dermal dendritic cells as the probable principal source of IL23.

Comment

This elegant series shows that TRPV1+ nociceptors in skin drive local skin inflammation and psoriasiform acanthosis in response to imiquimod activation of toll-like receptors through activation of skin resident γδT cells. This work demonstrates how localized inflammation can be driven by a nociceptive neural response that likely also causes itching and discomfort. The prominent role of γδT cells is interesting although of unclear significance — these cells are much less common in human skin. Nevertheless, these data point toward neurons as a new class of target for modulating skin inflammation.

Editor Disclosures at Time of Publication

  • Disclosures for Kenneth Y. Tsai, MD, PhD at time of publication Grant / research support NIH/NIAMS; AACR Landon Foundation; NIH/NCI; Duncan Family Institute Editorial Boards Journal of the American Academy of Dermatology (Member)

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