Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide ?-CGRP Modulates Group 2 Innate Lymphoid Cell Responses.

ABSTRACT: Signaling abnormalities in immune responses in the small intestine can trigger chronic type 2 inflammation involving interaction of multiple immune cell types. To systematically characterize this response, we analyzed 58,067 immune cells from the mouse small intestine by single-cell RNA sequencing (scRNA-seq) at steady state and after induction of a type 2 inflammatory reaction to ovalbumin (OVA). Computational analysis revealed broad shifts in both cell-type composition and cell programs in response to the inflammation, especially in group 2 innate lymphoid cells (ILC2s). Inflammation induced the expression of exon 5 of Calca, which encodes the alpha-calcitonin gene-related peptide (?-CGRP), in intestinal KLRG1+ ILC2s. ?-CGRP antagonized KLRG1+ ILC2s proliferation but promoted IL-5 expression. Genetic perturbation of ?-CGRP increased the proportion of intestinal KLRG1+ ILC2s. Our work highlights a model where ?-CGRP-mediated neuronal signaling is critical for suppressing ILC2 expansion and maintaining homeostasis of the type 2 immune machinery.

SUBMITTER: Xu H 

PROVIDER: S-EPMC6991097 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature