First Author | Xu H | Year | 2019 |
Journal | Immunity | Volume | 51 |
Issue | 4 | Pages | 696-708.e9 |
PubMed ID | 31618654 | Mgi Jnum | J:282494 |
Mgi Id | MGI:6381051 | Doi | 10.1016/j.immuni.2019.09.004 |
Citation | Xu H, et al. (2019) Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide alpha-CGRP Modulates Group 2 Innate Lymphoid Cell Responses. Immunity 51(4):696-708.e9 |
abstractText | 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 (alpha-CGRP), in intestinal KLRG1(+) ILC2s. alpha-CGRP antagonized KLRG1(+) ILC2s proliferation but promoted IL-5 expression. Genetic perturbation of alpha-CGRP increased the proportion of intestinal KLRG1(+) ILC2s. Our work highlights a model where alpha-CGRP-mediated neuronal signaling is critical for suppressing ILC2 expansion and maintaining homeostasis of the type 2 immune machinery. |