1. A chemogenetic screen reveals that Trpv1-expressing neurons control regulatory T cells in the gut.
- Author
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Zhu Y, Meerschaert KA, Galvan-Pena S, Bin NR, Yang D, Basu H, Kawamoto R, Shalaby A, Liberles SD, Mathis D, Benoist C, and Chiu IM
- Subjects
- Animals, Mice, Cholinergic Neurons metabolism, Gastrointestinal Microbiome, Intestines immunology, Intestines cytology, Macrophages immunology, Macrophages metabolism, Mice, Inbred C57BL, Nociception, Nuclear Receptor Subfamily 1, Group F, Member 3 metabolism, Calcitonin Gene-Related Peptide metabolism, Calcitonin Gene-Related Peptide genetics, Ganglia, Spinal metabolism, Ganglia, Spinal cytology, Neuroimmunomodulation, Nociceptors metabolism, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Th17 Cells immunology, TRPV Cation Channels metabolism, TRPV Cation Channels genetics
- 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 (T
H 17)-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.- Published
- 2024
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