New Evidence that Peripheral Nerves Sense Infection and Drive IL-23 Production by Skin Dendritic Cells

peripheral nerves stimulate IL-23

In a new study published in the journal Immunity, Sakeen Kashem and colleagues from the University of Minnesota, Minneapolis, MN, USA report that in the murine skin, IL-23, derived from CD301b+ DCs drives IL-17A production by γδ T cells, and this cytokine network is required to establish resistance to cutaneous candidiasis.

Interleukin (IL)-23 is a major pro-inflammatory cytokine that drives IL-17 production by tissue-resident lymphocytes. Recent research indicates that the IL-23→IL-17 axis plays a crucial role in chronic inflammation and several autoimmune diseases.

A recent Nature study provided new insights into the connection between the peripheral nervous system, nociception and innate immunity. It indicated that TRPV1 (transient receptor potential vanilloid 1) sensory nerves trigger IL-23 output in psoriasis-like inflammation, and that dendritic cells (DCs) are in direct contact with sensory nerves. In this IL-23-mediated imiquimod-induced skin inflammation model, sensory neurons induced and controled IL-23 production by nearby DCs.

The new Immunity study indicates that sensory nociceptive neurons are able to directly ‘sense’ fungal agents such as Candida albicans. Furthermore, the study shows that calcitonin gene related peptide (CGRP), released from TRPV1-positive fibers is able to up-regulate IL-23 production by CD301b+ DCs, which in turn drives IL-17 production by γδ T cells.

Thus, Kashem et al., provide a model where pain-sensing neurons, neuropeptides such as CGRP, skin innate and immune cells, and cytokines as IL-23 and IL-17 are involved in a local neural-immune response delivering resistance to skin infections such as candidiasis.

The study may have important implications for autoimmune diseases in the skin, and/or the development of new antimicrobial/antifungal therapeutic strategies.

Source: Immunity, 2015, 43:515-26. doi: 10.1016/j.immuni.2015.08.016
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