%0 Journal Article
%T A chemogenetic screen reveals that Trpv1-expressing neurons control regulatory T cells in the gut.
%A Zhu Y
%A Meerschaert KA
%A Galvan-Pena S
%A Bin NR
%A Yang D
%A Basu H
%A Kawamoto R
%A Shalaby A
%A Liberles SD
%A Mathis D
%A Benoist C
%A Chiu IM
%J Science
%V 385
%N 6708
%D 2024 Aug 2
%M 39088603
%F 63.714
%R 10.1126/science.adk1679
%X Neuroimmune cross-talk participates in intestinal tissue homeostasis and host defense. However, the matrix of interactions between arrays of molecularly defined neuron subsets and of immunocyte lineages remains unclear. We used a chemogenetic approach to activate eight distinct neuronal subsets, assessing effects by deep immunophenotyping, microbiome profiling, and immunocyte transcriptomics in intestinal organs. Distinct immune perturbations followed neuronal activation: Nitrergic neurons regulated T helper 17 (TH17)-like cells, and cholinergic neurons regulated neutrophils. Nociceptor neurons, expressing Trpv1, elicited the broadest immunomodulation, inducing changes in innate lymphocytes, macrophages, and RORγ+ regulatory T (Treg) cells. Neuroanatomical, genetic, and pharmacological follow-up showed that Trpv1+ neurons in dorsal root ganglia decreased Treg cell numbers via the neuropeptide calcitonin gene-related peptide (CGRP). Given the role of these neurons in nociception, these data potentially link pain signaling with gut Treg cell function.