Single cell RNA sequencing reveals regional heterogeneity of hepatobiliary innate lymphoid cells in a tissue-enriched fashion

Anna L. Peters, Zhenhua Luo, Jun Li, Reena Mourya, Yunguan Wang, Phillip Dexheimer, Pranav Shivakumar, Bruce Aronow, Jorge A. Bezerra

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

IL-33 promotes type 2 immunity, epithelial repair, and tissue fibrosis by activating group 2 innate lymphoid cells (ILC2). ILC2 lack all known surface markers of mature T, B, NK, and myeloid cell lineages (Lin neg ), express the IL-33 receptor ST2, and release type 2 cytokines which contribute to cholangiocyte proliferation and activation of hepatic stellate cells. This pathway results in massive proliferation of the extrahepatic bile duct (EHBD) but also exacerbates liver fibrosis, suggesting that there may be tissue-specific subpopulations of IL-33induced ILC. To determine the tissue-specific subsets of ILC in the hepatobiliary system, we analyzed CD45 + Lin neg mononuclear cells from IL-33 treated adult Balb/c mouse liver or EHBD by single cell RNA sequencing. Principal component analysis identified 6 major CD45 + Lin neg cell classes, two of which were restricted to the EHBD. One of these classes, biliary immature myeloid (BIM) cells, was predicted to interact with ILC2 by a network of shared receptor-ligand pairs. BIM highly expressed Gp49 and ST2 receptors on the cell surface while lacking surface expression of markers for mature myeloid cells. In conclusion, single cell RNA sequencing identified IL-33 responsive cell groups regionally confined to the liver or extrahepatic bile duct, including a novel population of CD45 + Lin neg Gp49-expressing mononuclear cells.

Original languageEnglish (US)
Article numbere0215481
JournalPloS one
Volume14
Issue number4
DOIs
StatePublished - Apr 2019
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Single cell RNA sequencing reveals regional heterogeneity of hepatobiliary innate lymphoid cells in a tissue-enriched fashion'. Together they form a unique fingerprint.

Cite this