Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses
Author(s)Xu, Heping; Ding, Jiarui; Porter, Caroline; Wallrapp, Antonia; Tabaka, Marcin; Ma, Sai; Fu, Shujie; Guo, Xuanxuan; Riesenfeld, Samantha J.; Su, Chienwen; Dionne, Danielle; Nguyen, Lan T.; Lefkovith, Ariel; Ashenberg, Orr; Burkett, Patrick R.; Shi, Hai Ning; Rozenblatt-Rosen, Orit; Graham, Daniel B.; Kuchroo, Vijay K.; Regev, Aviv; Xavier, Ramnik J.; ... Show more Show less
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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.
DepartmentBroad Institute of MIT and Harvard; Massachusetts Institute of Technology. Department of Biology
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
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