A chemogenetic screen reveals that Trpv1-expressing neurons control regulatory T cells in the gut

• 成果类型: Article
• 署名作者: Zhu, Yangyang; Meerschaert, Kimberly A.; Galvan-Pena, Silvia; Bin, Na-Ryum; Yang, Daping; Basu, Himanish; Kawamoto, Ryo; Shalaby, Amre; Liberles, Stephen D.; Mathis, Diane; Benoist, Christophe; Chiu, Isaac M.
• 署名单位: Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9788
• DOI: 10.1126/science.adk1679
• 发表日期: 2024-08-02
• 关键词: innate lymphoid-cells; gene-related peptide; sensory neurons; muscularis macrophages; nervous-system; receptor; pain; innervation; microbiota; physiology

摘要

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 ROR gamma(+) regulatory T (T-reg) cells. Neuroanatomical, genetic, and pharmacological follow-up showed that Trpv1(+) neurons in dorsal root ganglia decreased T-reg 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 T-reg cell function.