Extended Data Fig. 10: Convergence of neuronal-epithelial-immune sensing promotes type 2 inflammation.
From: Neuro-epithelial circuits promote sensory convergence and intestinal immunity
Model: Upon activation, TRPV1+ nociceptors release sensory neuropeptide CGRP, leading to (1) epithelial progenitor differentiation into intestinal tuft cells as well as (2) tuft cell activation with upregulated Tuft-2 gene signatures and effector molecules such as cysteinyl leukotrienes, prostaglandins and alarmin cytokines, via the epithelial CGRP receptor complex CALCRL and RAMP1. These tuft cell effector molecules expand and activate (3) ILC2s and CD4+ Th2 cells, that release cytokines including IL-4, IL-5 and IL-13 that further drive type 2 inflammation and immunity, goblet cell mucus secretion, epithelial turnover and smooth muscle contractions (4). In the context of helminth infection, these processes help drive expulsion of gastrointestinal nematodes (5). This ilustration was created in BioRender.Emanuel, E. (2025) https://biorender.com/b1xymo3.
