TY - JOUR AU - Lee, Ha-Na AU - Tian, Linjie AU - Bouladoux, Nicolas AU - Davis, Jacquice AU - Quinones, Mariam AU - Belkaid, Yasmine AU - Coligan, John E. AU - Krzewski, Konrad T1 - Dendritic cells expressing immunoreceptor CD300f are critical for controlling chronic gut inflammation PY - 2017/05/01/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI89531 VL - 127 IS - 5 UR - https://doi.org/10.1172/JCI89531 SP - 1905 EP - 1917 PB - The American Society for Clinical Investigation ER -