A role for interleukin 17A in IBD-related neuroplasticity

Abstract

Background

Changes to the structure and function of the innervation of the gut contribute to symptom generation in inflammatory bowel diseases (IBD). However, delineation of the mechanisms of these effects has proven difficult. Previous work on sympathetic neurons identified interleukin (IL)-17A as a novel neurotrophic cytokine. Since IL-17A is involved in IBD pathogenesis, we tested the hypothesis that IL-17A contributes to neuroanatomical remodeling during IBD.

Methods

Immunohistochemistry for tyrosine hydroxylase was used to identify sympathetic axons in mice with dextran sulphate sodium (DSS)-induced colitis and controls. Axon outgrowth from sympathetic neurons in response to incubation in cytokines or endoscopic patient biopsy supernatants was quantified.

Key Results

DSS-induced colitis led to an increase in tyrosine hydroxylase immunoreactivity in the inflamed colon but not the spleen. Colonic supernatants from mice with colitis and biopsy supernatants from Crohn's disease patients increased axon outgrowth from mouse sympathetic neurons compared to supernatants from uninflamed controls. An antibody that neutralized IL-17A blocked the ability of DSS-induced colitis and Crohn's disease supernatants to induce axon extension.

Conclusions and Inferences

These findings identify IL-17A as a potential mediator of neuroanatomical remodeling of the gut innervation during IBD.

Neuroplasticity during IBD may contribute to symptom generation but the mechanisms involved remain incompletely understood. This study identifies IL-17A as a potential mediator of sympathetic axon remodelling in a model of IBD and in response to IBD biopsy supernatants.

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