CD300f-expressing dendritic cells are critical for controlling chronic gut inflammation

Abstract

Abstract Pro-inflammatory cytokine overproduction and excessive cell death, coupled with the impaired apoptotic cell clearance, have been implicated as causes for failure to resolve gut inflammation in inflammatory bowel diseases. CD300f (CLM-1), a cell surface receptor that recognizes phosphatidylserine exposed on apoptotic cells, is important for immune homeostasis. In this study, we show that CD300f -expressing dendritic cells play a crucial role in regulating gut inflammatory responses. CD300f-deficient mice fail to resolve colonic inflammation, due to defects in dendritic cell function associated with abnormal apoptotic cell build-up in the gut. CD300f-deficient dendritic cells display hyperactive phagocytosis of apoptotic cells, which stimulates them to excessive TNF-α secretion. This, in turn, induces secondary IFN-γ overproduction by colonic T cells, leading toprolonged gut inflammation. Our data highlight a previously unappreciated role of dendritic cells in controlling gut homeostasis, and show that CD300f regulation of apoptotic cell uptake is essential for suppressing overactive dendritic cell-mediated inflammatory responses, thereby controlling the development of chronic gut inflammation.