T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Nov 6

PMID 30392957

Citations 287

Authors

Moshe Biton

Adam L Haber

Noga Rogel

Grace Burgin

Semir Beyaz

Alexandra Schnell

Orr Ashenberg

Chien-Wen Su

Christopher Smillie

Karthik Shekhar

Zuojia Chen

Chuan Wu

Jose Ordovas-Montanes

David Alvarez

Rebecca H Herbst

Mei Zhang

Itay Tirosh

Danielle Dionne

Lan T Nguyen

Michael E Xifaras

Alex K Shalek

Ulrich H von Andrian

Daniel B Graham

Orit Rozenblatt-Rosen

Hai Ning Shi

Vijay Kuchroo

Omer H Yilmaz

Aviv Regev

Ramnik J Xavier

Affiliations

Soon will be listed here.

Abstract

In the small intestine, a niche of accessory cell types supports the generation of mature epithelial cell types from intestinal stem cells (ISCs). It is unclear, however, if and how immune cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5 ISCs. We show that MHCII Lgr5 ISCs are non-conventional antigen-presenting cells in co-cultures with CD4 T helper (Th) cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5 ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory cells and cytokines reduce it. In vivo genetic perturbation of Th cells or MHCII expression on Lgr5 ISCs impacts epithelial cell differentiation and IEC fate during infection. These interactions between Th cells and Lgr5 ISCs, thus, orchestrate tissue-wide responses to external signals.

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