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A chemogenetic screen for neuroimmune interplay reveals Trpv1+ neuron control of Tregs in the gut

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): mouse metagenome

PROVIDER: GSE267709 | GEO | 2026/09/01

REPOSITORIES: GEO

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A chemogenetic screen for neuroimmune interplay reveals Trpv1+ neuron control of Tregs in the gut [Batch2]

Project description:Neuroimmune crosstalk 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 utilized 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: Nos1+nitrergic neurons regulated Th17-like cells, and Chat+cholinergic neurons regulated neutrophils. Trpv1+ nociceptor neurons elicitinged the broadest immunomodulation, inducing changes in innate lymphocytes, macrophages, and RORγ+ T regulatory (Treg) cells. Further nNeuroanatomical, genetic and pharmacological analysis followup showed that Trpv1+ neurons in dorsal root ganglia decreased Treg cell numbers via the neuropeptide CGRP. Given the role of these neurons in nociception, these data potentially link pain signaling with gut Treg function.

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A chemogenetic screen for neuroimmune interplay reveals Trpv1+ neuron control of Tregs in the gut [Batch1]

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A chemogenetic screen for neuroimmune interplay reveals Trpv1+ neuron control of Tregs in the gut

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A chemogenetic screen for neuro-immune interactions in the gut: Trpv1+ nociceptor neurons control T regulatory cells

Project description:Neuroimmune crosstalk is critical for intestinal and tissue homeostasis. Yet the role of molecularly distinct subsets of gut-innervating neurons in regulating the activity of gut immunocytes, and the mechanisms of this neuroimmune signaling remain unclear. Here, we performed a chemogenetic and flow cytometry-based analysis of mice targeting eight different peripheral neuron subsets to assess how gut immunocytes are altered following neural activation. We found that distinct neurons modulated discreet anatomical populations of immunocytes in the gut in ileum, cecum, and colon. Nos1+ neuron activation decreased the percentage of RORg+ ileal conventional CD4+ T cells, whereas ChAT+ neuron activation decreased ileal neutrophils. Trpv1+ neuron activation displayed the most robust immunomodulatory phenotype, causing downregulation of RORg+ T regulatory cells in the colon and cecum. The immune cells exhibited decreased proliferation, enhanced cell stress, and altered cell activation markers. Further genetic and pharmacological approaches showed that spinal afferent Trpv1+ neurons specifically decreased Treg cells by signaling via the neuropeptide CGRP. Our study provided a comprehensive understanding of neuro-immune interactions, revealing a role for mechanisms by which Trpv1+ neurons regulate gut Treg cells.

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PhosphoRiboTrap sequencing data of chemogenetic MCH neuron activation

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