| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Gill, Navkiran Roberts, Morgan E. Kum, Winnie W. S. Harder, Kenneth W. Huang, Morris Finlay, B. Brett Krebs, Danielle L. Fan, Xueling Bishop, Jennifer L. Priatel, John J. Beer, Jennifer L. |
| Description |
Author Affiliation: Roberts ME ( Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada); Bishop JL ( Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada); Fan X ( Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada); Beer JL ( Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada); Kum WW ( Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada); Krebs DL ( Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada); Huang M ( Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada); Gill N ( Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada); Priatel JJ ( Child and Family Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.); Finlay BB ( Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada); Harder KW ( Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada) |
| Abstract |
The Lyn tyrosine kinase governs the development and function of various immune cells, and its dysregulation has been linked to malignancy and autoimmunity. Using models of chemically induced colitis and enteric infection, we show that Lyn plays a critical role in regulating the intestinal microbiota and inflammatory responses as well as protection from enteric pathogens. Lyn(-/-) mice were highly susceptible to dextran sulfate sodium (DSS) colitis, characterized by significant wasting, rectal bleeding, colonic pathology, and enhanced barrier permeability. Increased DSS susceptibility in Lyn(-/-) mice required the presence of T but not B cells and correlated with dysbiosis and increased IFN-γ(+) and/or IL-17(+) colonic T cells. This dysbiosis was characterized by an expansion of segmented filamentous bacteria, associated with altered intestinal production of IL-22 and IgA, and was transmissible to wild-type mice, resulting in increased susceptibility to DSS. Lyn deficiency also resulted in an inability to control infection by the enteric pathogens Salmonella enterica serovar Typhimurium and Citrobacter rodentium. Lyn(-/-) mice exhibited profound cecal inflammation, bacterial dissemination, and morbidity following S. Typhimurium challenge and greater colonic inflammation throughout the course of C. rodentium infection. These results identify Lyn as a key regulator of the mucosal immune system, governing pathophysiology in multiple models of intestinal disease. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
10 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-11-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Colitis Immunology Dysbiosis Enterobacteriaceae Infections Salmonella Infections Src-family Kinases Animals B-lymphocytes Microbiology Citrobacter Rodentium Pathogenicity Chemically Induced Pathology Dextran Sulfate Disease Susceptibility Genetics Gene Expression Immunoglobulin A Metabolism Interferon-gamma Interleukin-17 Interleukins Intestinal Mucosa Mice Mice, Knockout Microbiota Salmonella Typhimurium Severity Of Illness Index T-lymphocytes Deficiency Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
