Figure 1. Chemogenetic silencing of TRPV1⁺ nociceptors lead to enhanced susceptibility to DSS-induced colitis.

(A, B) Naïve and inflamed mouse colons from Trpv1-Cre/tdTomato reporter mice, stained for βIII-tubulin (green) and DAPI (white). S, submucosa; M, muscularis. Yellow arrows show representative TRPV1⁺ nociceptor innervation. (C to H) Disease and recovery of DSS-treated TRPV1^hM4Di and their littermate control mice were monitored by daily weight loss (C), clinical disease score (D), colon length (E) and H&E staining of the distal colon on day 10 (F). (G, H) PAS staining of the distal colon and analysis of PAS⁺ goblet cells per crypt. (I, J) Frequency of colonic neutrophils from mice in (C) on day 10, pre-gated on live, CD45⁺ events. (K to M) Flow cytometric analysis of T cell cytokine production from mice in (C) on day 10, pre-gated on live, CD45⁺ CD4⁺ events. (N to P) Disease and recovery of DSS-treated Trpv1-Cre mice infected with AAV9 viruses were monitored by daily weight loss (N), colon length (O) and H&E staining of the distal colon on day 10 (P). Scale bars = 50 μm in (A), (B), (F) and (P), and 100 μm in (G). Data are representative of three independent experiments with n=4 to 5 mice per group in (C to J, N to Q). Data are pooled from three independent experiments with n=4–5 mice per group in each experiment in (L) and (M). Data are Mean ± SEM. ns, not significant, * P < 0.05, ** P < 0.01, *** P < 0.001.