First Evidence of Sensory Nerves Driving Interleukin-23 Production in Skin: A Breakthrough in Psoriasis Research?

First Evidence of Sensory Nerves Driving Interleukin-23 Production in Skin: A Breakthrough in Psoriasis Research?

A study published in the June 05, 2014 issue of Nature magazine indicates that sensory nerve-driven interleukin-(IL)-23 production by dermal dendritic cells (DDCs) contributes to psoriasis-like inflammation. These findings may represent a breakthrough in psoriasis research and the understanding of the pathogenesis of this skin disease.

The IL-23IL-17 axis plays a major role in the development and progression of several inflammatory diseases, including psoriasis.

The skin is highly innervated by sensory and autonomic nerves loaded with a plethora of neuropeptides and neurotransmitters, which may be released upon central or peripheral stimulation.

Psoriasis is among a group of skin diseases long recognized to be influenced by neuronal and neurohormonal factors, and triggered by psychological stress.

In the Nature study Lorena Riol-Blanco and colleagues from the Department of Microbiology and Immunobiology, Harvard Medical School, USA and the Institute for Biomedical Research, University College London, UK, found that in the skin of mice approximately 75% of DDCs are in direct contact or in close proximity to sensory nerves.

When using pharmacological or genetic ablation of nociceptors, they observed that DDCs failed to produce IL-23 in an imiquimod model of psoriasiform skin inflammation.

The authors propose a model of skin neuroimmune-mediated inflammation, where a subset of sensory neurons expressing the ion channels TRPV1 (transient receptor potential vanilloid 1) and Nav1.8 may play a major role in triggering IL-23 production by nearby DDCs.

Thus, IL-23 in turn may act on skin-resident T cells to induce IL-17 and IL-22, and precipitating the recruitment of neutrophils and monocytes that drive psoriasiform skin inflammation.

According to the authors these findings may suggest new strategies for the treatment of inflammatory diseases in the skin.

Source: Nature, 2014 Jun 5;510(7503):157-61. doi: 10.1038/nature13199. Epub 2014 Apr 23.

Read more: Nature

Source: Cover Image: Photo montage; Left: Interleukin 23, alpha subunit p19. Structure of protein IL-23A. Based on PyMOL rendering of PDB 3D85. Author: Pleiotrope. Credit: Wikimedia Commons. Right: Nociceptor activation by acid. Public domain. Credit: Department of Pharmacology, University of Cambridge; http://www.phar.cam.ac.uk/research/Smith/Research%20Interest




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