Abstract
The role of p53 in tumor suppression has been extensively studied and well-established. However, the role of p53 in parasitic infections and the intestinal type 2 immunity is unclear. Here, we report that p53 is crucial for intestinal type 2 immunity in response to the infection of parasites, such as Tritrichomonas muris and Nippostrongylus brasiliensis. Mechanistically, p53 plays a critical role in the activation of the tuft cell-IL-25-type 2 innate lymphoid cell circuit, partly via transcriptional regulation of Lrmp in tuft cells. Lrmp modulates Ca2+ influx and IL-25 release, which are critical triggers of type 2 innate lymphoid cell response. Our results thus reveal a previously unrecognized function of p53 in regulating intestinal type 2 immunity to protect against parasitic infections, highlighting the role of p53 as a guardian of immune integrity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Line, Tumor
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Eosinophils / immunology
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Eosinophils / parasitology
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Gene Expression Regulation
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Goblet Cells / immunology
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Goblet Cells / parasitology
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Host-Parasite Interactions / immunology
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Humans
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Immunity, Innate / immunology*
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Intestine, Small / immunology
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Intestine, Small / metabolism
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Intestine, Small / parasitology
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Intestines / immunology*
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Intestines / parasitology
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Membrane Proteins / genetics
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Membrane Proteins / immunology
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nippostrongylus / immunology*
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Nippostrongylus / physiology
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Parasitic Diseases / immunology*
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Parasitic Diseases / metabolism
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Parasitic Diseases / parasitology
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Tritrichomonas / immunology*
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Tritrichomonas / physiology
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / immunology*
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Tumor Suppressor Protein p53 / metabolism
Substances
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Lrmp protein, mouse
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Membrane Proteins
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Tumor Suppressor Protein p53