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Cell. 2016 Aug 25;166(5):1231-1246.e13. doi: 10.1016/j.cell.2016.07.043. Epub 2016 Aug 18.

The Spectrum and Regulatory Landscape of Intestinal Innate Lymphoid Cells Are Shaped by the Microbiome.

Author information

1
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
2
Innate Immunity Unit, Institut Pasteur, 75015 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1223 Paris, France.
3
Biological Services Unit, Weizmann Institute of Science, Rehovot 76100, Israel.
4
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
5
Institut Pasteur, Microenvironment & Immunity Unit, 75724 Paris, France; INSERM U1224, 75724 Paris, France.
6
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
7
Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
8
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: eran.elinav@weizmann.ac.il.
9
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: ido.amit@weizmann.ac.il.

Abstract

Innate lymphoid cells (ILCs) are critical modulators of mucosal immunity, inflammation, and tissue homeostasis, but their full spectrum of cellular states and regulatory landscapes remains elusive. Here, we combine genome-wide RNA-seq, ChIP-seq, and ATAC-seq to compare the transcriptional and epigenetic identity of small intestinal ILCs, identifying thousands of distinct gene profiles and regulatory elements. Single-cell RNA-seq and flow and mass cytometry analyses reveal compartmentalization of cytokine expression and metabolic activity within the three classical ILC subtypes and highlight transcriptional states beyond the current canonical classification. In addition, using antibiotic intervention and germ-free mice, we characterize the effect of the microbiome on the ILC regulatory landscape and determine the response of ILCs to microbial colonization at the single-cell level. Together, our work characterizes the spectrum of transcriptional identities of small intestinal ILCs and describes how ILCs differentially integrate signals from the microbial microenvironment to generate phenotypic and functional plasticity.

KEYWORDS:

epigenome; innate lymphoid cells; microbiota; single-cell transcriptomics

PMID:
27545347
DOI:
10.1016/j.cell.2016.07.043
[Indexed for MEDLINE]
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