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

Heping Xu, Jiarui Ding, Caroline B.M. Porter, Antonia Wallrapp, Marcin Tabaka, Sai Ma, Shujie Fu, Xuanxuan Guo, Samantha J. Riesenfeld, Chienwen Su, Danielle Dionne, Lan T. Nguyen, Ariel Lefkovith, Orr Ashenberg, Patrick R. Burkett, Hai Ning Shi, Orit Rozenblatt-Rosen, Daniel B. Graham, Vijay K. Kuchroo, Aviv RegevRamnik J. Xavier

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

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.

Original languageEnglish
Pages (from-to)696-708.e9
JournalImmunity
Volume51
Issue number4
DOIs
StatePublished - 15 Oct 2019
Externally publishedYes

Keywords

  • CGRP
  • allergic inflammation
  • batch effect correction
  • intestinal immune cell atlas
  • neuro-immune interaction
  • neuropeptides
  • scRNA-seq
  • single cell genomics
  • topic model
  • type 2 innate lymphoid cells

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