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

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.