Mapping neuroimmune interactions in the gut

Abstract

New research has mapped neuroimmune interactions in the mouse gut, revealing that TRPV1-expressing nociceptor neurons (involved in visceral pain) control and suppress regulatory T (T_reg) cells in the gut, increasing susceptibility to colitis in mouse models. The findings potentially link pain signalling with immunomodulatory mechanisms in the gut.

In their screen, eight distinct neuronal subsets were activated in mice and mapped. Distinct immune perturbations were observed following this activation: nitrergic neurons (NOS1 expression) regulated T helper 17-like cells in the ileum; cholinergic neurons (express choline acetyltransferase) regulated ileal neutrophils; and nociceptor neurons (TRPV1 expression) regulated a range of cell types including type 2 innate lymphoid cells, activated CD8⁺ T cells, macrophages and RORγ T_reg cells. Examining the nociceptor neurons in more detail revealed that TRPV1⁺ neurons in the dorsal root ganglia suppressed RORγ⁺ T_reg cells in the colon via calcitonin gene-related peptide, which was mediated via the receptor RAMP1–CALCRL. Importantly, TRPV1⁺ neuron activation and subsequent downregulation of T_reg cells resulted in increased susceptibility to intestinal inflammation in mice (via Citrobacter infection and induction by administration of dextran sodium sulfate).