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Nat Immunol. 2015 Nov;16(11):1124-33. doi: 10.1038/ni.3272. Epub 2015 Sep 28.

Runx3 specifies lineage commitment of innate lymphoid cells.

Author information

1
Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
2
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
3
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
4
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
5
Medical Scientist Training Program, Washington University School of Medicine, St. Louis, Missouri, USA.

Abstract

Subsets of innate lymphoid cells (ILCs) reside in the mucosa and regulate immune responses to external pathogens. While ILCs can be phenotypically classified into ILC1, ILC2 and ILC3 subsets, the transcriptional control of commitment to each ILC lineage is incompletely understood. Here we report that the transcription factor Runx3 was essential for the normal development of ILC1 and ILC3 cells but not of ILC2 cells. Runx3 controlled the survival of ILC1 cells but not of ILC3 cells. Runx3 was required for expression of the transcription factor RORγt and its downstream target, the transcription factor AHR, in ILC3 cells. The absence of Runx3 in ILCs exacerbated infection with Citrobacter rodentium. Therefore, our data establish Runx3 as a key transcription factor in the lineage-specific differentiation of ILC1 and ILC3 cells.

PMID:
26414766
PMCID:
PMC4618046
DOI:
10.1038/ni.3272
[Indexed for MEDLINE]
Free PMC Article

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