{Reference Type}: Journal Article
{Title}: A chemogenetic screen reveals that Trpv1-expressing neurons control regulatory T cells in the gut.
{Author}: Zhu Y;Meerschaert KA;Galvan-Pena S;Bin NR;Yang D;Basu H;Kawamoto R;Shalaby A;Liberles SD;Mathis D;Benoist C;Chiu IM;
{Journal}: Science
{Volume}: 385
{Issue}: 6708
{Year}: 2024 Aug 2
{Factor}: 63.714
{DOI}: 10.1126/science.adk1679
{Abstract}: 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.