2017
J Clin Invest. 2017 May 1;127(5):1905-1917. doi: 10.1172/JCI89531. Epub 2017 Apr 17.
Dendritic cells expressing immunoreceptor CD300f are critical for controlling chronic gut inflammation.
Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland, USA. NIAID Microbiome Program, Mucosal Immunology Section, and Bioinformatics and Computational Bioscience Branch, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Service type: Knockout mice
Abstract
Proinflammatory cytokine overproduction and excessive cell death, coupled with impaired clearance of apoptotic cells, have been implicated as causes of failure to resolve gut inflammation in inflammatory bowel diseases. Here we have found that dendritic cells expressing the apoptotic cell-recognizing receptor CD300f play a crucial role in regulating gut inflammatory responses in a murine model of colonic inflammation. CD300f-deficient mice failed to resolve dextran sulfate sodium-induced colonic inflammation as a result of defects in dendritic cell function that were associated with abnormal accumulation of apoptotic cells in the gut. CD300f-deficient dendritic cells displayed hyperactive phagocytosis of apoptotic cells, which stimulated excessive TNF-α secretion predominantly from dendritic cells. This, in turn, induced secondary IFN-γ overproduction by colonic T cells, leading to prolonged gut inflammation. Our data highlight a previously unappreciated role for dendritic cells in controlling gut homeostasis and show that CD300f-dependent regulation of apoptotic cell uptake is essential for suppressing overactive dendritic cell-mediated inflammatory responses, thereby controlling the development of chronic gut inflammation.
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