title: Lyn activity protects mice from DSS colitis and regulates the production of IL-22 from innate lymphoid cells.
abstract: Intestinal homeostasis requires a complex balance of interactions between diverse resident microbial communities, the intestinal epithelium, and the underlying immune system. We show that the Lyn tyrosine kinase, a critical regulator of immune cell function and pattern-recognition receptor (PRR) responses, has a key role in controlling gastrointestinal inflammation. Lyn⁻/⁻ mice were highly susceptible to dextran sulfate sodium (DSS)-induced colitis, whereas Lyn gain-of-function (Lyn(up)) mice exhibited attenuated colitis during acute and chronic models of disease. Lyn(up) mice were hypersensitive to lipopolysaccharide (LPS), driving enhanced production of cytokines and factors associated with intestinal barrier function, including interleukin (IL)-22. Oral administration of LPS was sufficient to protect antibiotic-treated Lyn(up) but not wild-type mice from DSS, highlighting how Lyn-dependent changes in the nature/magnitude of PRR responses can impact intestinal health. Furthermore, protection from DSS-induced colitis and increased IL-22 production in response to LPS did not depend on the adaptive immune system, with increased innate lymphoid cell-derived IL-22 correlating with Lyn activity in dendritic cells. These data reveal a key role for Lyn in the regulation of innate immune responses and control of intestinal inflammation.
authors.affiliation: Department of Microbiology and Immunology, I Research Group, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Bishop
authors.affiliation: Department of Microbiology and Immunology, I Research Group, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: M E
authors.initials: ME
authors.lastname: Roberts
authors.affiliation: Department of Microbiology and Immunology, I Research Group, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Beer
authors.affiliation: Department of Microbiology and Immunology, I Research Group, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Immunology, I Research Group, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: M K
authors.initials: MK
authors.lastname: Chehal
authors.affiliation: Department of Microbiology and Immunology, I Research Group, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Fan
authors.affiliation: Inflammation and Immunology Research Unit, Biotherapeutics Research and Development, Pfizer Worldwide R and D, Cambridge, Masschusetts, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Fouser
authors.affiliation: Inflammation and Immunology Research Unit, Biotherapeutics Research and Development, Pfizer Worldwide R and D, Cambridge, Masschusetts, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Ma
authors.affiliation: Department of Laboratory Medicine and Pathology, Division of Anatomical Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: J T
authors.initials: JT
authors.lastname: Bacani
authors.affiliation: Department of Microbiology and Immunology, I Research Group, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: K W
authors.initials: KW
authors.lastname: Harder
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D007113:Immunity, Innate; D007378:Interleukins / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D016264:Dextran Sulfate; D007378:Interleukins; D008070:Lipopolysaccharides; D019061:src-Family Kinases; D000097043:Interleukin-22; C060902:lyn protein-tyrosine kinase
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