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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Ly / metabolism
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Cell Differentiation / immunology
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Cell Lineage / immunology
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Citrobacter rodentium / immunology
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Citrobacter rodentium / pathogenicity
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Core Binding Factor Alpha 3 Subunit / deficiency
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Core Binding Factor Alpha 3 Subunit / genetics
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Core Binding Factor Alpha 3 Subunit / metabolism*
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Core Binding Factor beta Subunit / deficiency
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Core Binding Factor beta Subunit / genetics
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Core Binding Factor beta Subunit / metabolism
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Enterobacteriaceae Infections / etiology
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Enterobacteriaceae Infections / immunology
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Immunity, Innate*
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Interleukin-7 Receptor alpha Subunit / metabolism
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Intestinal Mucosa / cytology
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Intestinal Mucosa / immunology
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Lymphocyte Subsets / cytology
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Lymphocyte Subsets / immunology*
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Lymphocyte Subsets / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Natural Cytotoxicity Triggering Receptor 1 / metabolism
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Nuclear Receptor Subfamily 1, Group F, Member 3 / deficiency
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Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
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Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
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Receptors, Aryl Hydrocarbon / genetics
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Receptors, Aryl Hydrocarbon / metabolism
Substances
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Ahr protein, mouse
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Antigens, Ly
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Basic Helix-Loop-Helix Transcription Factors
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Cbfb protein, mouse
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Core Binding Factor Alpha 3 Subunit
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Core Binding Factor beta Subunit
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Interleukin-7 Receptor alpha Subunit
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Natural Cytotoxicity Triggering Receptor 1
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Ncr1 protein, mouse
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Aryl Hydrocarbon
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Rorc protein, mouse
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Runx3 protein, mouse