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.
摘要
神经免疫交叉对话参与了肠道组织的稳态和宿主防御。然而，分子定义的神经元亚群阵列与免疫细胞系之间的相互作用机制仍不清楚。我们采用化学遗传学方法激活了八个不同的神经元亚群，并通过肠道器官的深度免疫分型、微生物组图谱分析和免疫细胞转录组学来评估其效果。神经元激活后出现了不同的免疫扰动：硝酸神经元调节T辅助细胞 17（TH17）样细胞，胆碱能神经元调节中性粒细胞。表达Trpv1的痛觉神经元可引起最广泛的免疫调节，诱导先天性淋巴细胞、巨噬细胞和RORγ+调节性T（Treg）细胞发生变化。神经解剖学、遗传学和药理学跟踪研究表明，背根神经节中的Trpv1+神经元通过神经肽降钙素基因相关肽（CGRP）减少了Treg细胞的数量。鉴于这些神经元在痛觉中的作用，这些数据可能将疼痛信号与肠道 Treg 细胞功能联系起来。
参考文献
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. A chemogenetic screen reveals that Trpv1-expressing neurons control regulatory T cells in the gut. Science. 2024 Aug 2;385(6708):eadk1679. doi: 10.1126/science.adk1679. Epub 2024 Aug 2. PMID: 39088603.
