T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation

Biton, M., Haber, A. L., Rogel, N., Burgin, G., Beyaz, S., Schnell, A., Ashenberg, O., Su, C. W., Smillie, C., Shekhar, K., Chen, Z., Wu, C., Ordovas-Montanes, J., Alvarez, D., Herbst, R. H., Zhang, M., Tirosh, I., Dionne, D., Nguyen, L. T., Xifaras, M. E., Shalek, A. K., von Andrian, U. H., Graham, D. B., Rozenblatt-Rosen, O., Shi, H. N., Kuchroo, V., Yilmaz, O. H., Regev, A., Xavier, R. J. (October 2018) T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation. Cell, 175 (5). pp. 1307-1320. ISSN 0092-8674

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.

Item Type:	Paper
Subjects:	Investigative techniques and equipment organism description > animal Investigative techniques and equipment > assays Investigative techniques and equipment > cell culture > cancer organoids Investigative techniques and equipment > cell culture organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell differentiation organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions Investigative techniques and equipment > assays > RNA-seq organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:	Beyaz, Semir
Communities:	CSHL labs > Beyaz lab CSHL Cancer Center Program > Cellular Communication in Cancer Program
Depositing User:	Matthew Dunn
Date:	26 October 2018
Date Deposited:	12 Nov 2018 20:43
Last Modified:	06 Feb 2024 21:22
PMCID:	PMC6239889
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/37352

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