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A chemogenetic screen reveals that Trpv1-expressing neurons control regulatory T cells in the gut
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 (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.
实验方法
产品清单
| 名称 | 品牌 | 货号 |
|---|---|---|
| Symphony流式细胞仪 | BD Biosciences | -- |
| Ti2转盘共聚焦显微镜 | Nikon | -- |
| Stellaris 8 FALCON共聚焦荧光系统 | Leica | -- |
| Leica Stellaris 8 FALCON共聚焦显微镜 | Leica | -- |
| 宽场显微镜 | Nikon | -- |
| 光纤内窥镜 | ZIBRA Corporation | -- |
| 手持式405 nm蓝紫色激光器 | -- | -- |
| Nanoinject II注射器 | Drummond | -- |
| 10X Chromium微流控仪器 | 10X Genomics | -- |
| Illumina MiSeq测序仪 | Illumina | -- |
| Illumina HiSeq X测序仪 | Illumina | -- |
| Qubit dsDNA HS检测试剂盒 | Thermo Fisher | -- |
| QIAquick PCR纯化试剂盒 | Qiagen | -- |
| 细胞滤网 | -- | -- |
| Silgard培养皿 | -- | -- |