Abstract
Innate lymphocyte populations play a central role in conferring protective immunity at the mucosal frontier. In this study, we demonstrate that T cell factor 1 (TCF-1; encoded by Tcf7), a transcription factor also important for NK and T cell differentiation, is expressed by multiple innate lymphoid cell (ILC) subsets, including GATA3(+) nuocytes (ILC2) and NKp46(+) ILCs (ILC3), which confer protection against lung and intestinal inflammation. TCF-1 was intrinsically required for the differentiation of both ILC2 and NKp46(+) ILC3. Loss of TCF-1 expression impaired the capacity of these ILC subsets to produce IL-5, IL-13, and IL-22 and resulted in crippled responses to intestinal infection with Citrobacter rodentium. Furthermore, a reduction in T-bet expression required for Notch-2-dependent development of NKp46(+) ILC3 showed a dose-dependent reduction in TCF-1 expression. Collectively, our findings demonstrate an essential requirement for TCF-1 in ILC2 differentiation and reveal a link among Tcf7, Notch, and Tbx21 in NKp46(+) ILC3 development.
Publication types
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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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Cell Differentiation / immunology
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Citrobacter rodentium / immunology
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Enterobacteriaceae Infections / immunology
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GATA3 Transcription Factor / metabolism
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Hepatocyte Nuclear Factor 1-alpha
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Inflammation / immunology
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Inflammation / microbiology
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Interleukin-13 / biosynthesis
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Interleukin-22
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Interleukin-5 / biosynthesis
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Interleukins / biosynthesis
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Intestines / immunology*
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Intestines / microbiology
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Killer Cells, Natural / metabolism*
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Lymphocyte Activation
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Mice
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Mice, Knockout
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Mucous Membrane / cytology
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Mucous Membrane / immunology
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Natural Cytotoxicity Triggering Receptor 1 / metabolism
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Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
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Receptor, Notch2 / metabolism
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T Cell Transcription Factor 1 / genetics
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T Cell Transcription Factor 1 / metabolism*
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T-Box Domain Proteins / biosynthesis
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T-Box Domain Proteins / immunology
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T-Lymphocytes / metabolism*
Substances
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Antigens, Ly
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GATA3 Transcription Factor
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Gata3 protein, mouse
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Hepatocyte Nuclear Factor 1-alpha
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Hnf1a protein, mouse
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Interleukin-13
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Interleukin-5
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Interleukins
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Natural Cytotoxicity Triggering Receptor 1
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Ncr1 protein, mouse
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Notch2 protein, mouse
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptor, Notch2
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T Cell Transcription Factor 1
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T-Box Domain Proteins
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T-box transcription factor TBX21