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：
神经免疫串扰参与肠组织稳态和宿主防御。然而,分子定义的神经元亚群和免疫细胞谱系阵列之间的相互作用矩阵仍不清楚。我们使用化学遗传学方法激活八个不同的神经元亚群，通过深度免疫表型评估效果，微生物组分析，和肠道器官中的免疫细胞转录组学。神经元激活后有明显的免疫扰动：一氧化氮神经元调节T辅助细胞17（TH17）样细胞，和胆碱能神经元调节中性粒细胞。伤害感受器神经元，表达Trpv1，引发最广泛的免疫调节，诱导先天淋巴细胞的变化，巨噬细胞，和RORγ+调节性T(Treg)细胞。神经解剖学,遗传,药理随访表明，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Treg细胞数量。鉴于这些神经元在伤害感受中的作用，这些数据可能将疼痛信号传导与肠道Treg细胞功能联系起来。
