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

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.
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