Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses
Name
Xu et al Immunity_2019.pdf
Description
Accepted version
Size
35.55 MB
Format
Adobe PDF
Checksum (MD5)
28581087a02ec2078d0c47696a264dd5
Author(s)
Xu, Heping
Ding, Jiarui
Porter, Caroline
Wallrapp, Antonia
Tabaka, Marcin
Ma, Sai
Fu, Shujie
Guo, Xuanxuan
Riesenfeld, Samantha J.
Su, Chienwen
Date Issued
October 2019
Journal
Immunity
Publisher
Elsevier BV
Citation
Xu, Heping et al. "Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses." Immunity 51, 4 (October 2019): P696-708.e9 © 2019 Elsevier
Version
Author's final manuscript
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 (α-CGRP), in intestinal KLRG1+ ILC2s. α-CGRP antagonized KLRG1+ ILC2s proliferation but promoted IL-5 expression. Genetic perturbation of α-CGRP increased the proportion of intestinal KLRG1+ ILC2s. Our work highlights a model where α-CGRP-mediated neuronal signaling is critical for suppressing ILC2 expansion and maintaining homeostasis of the type 2 immune machinery.
MIT Department
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.immuni.2019.09.004
