Dendritic cells expressing immunoreceptor CD300f are critical for controlling chronic gut inflammation
Ha-Na Lee ... John E. Coligan, Konrad Krzewski
Ha-Na Lee ... John E. Coligan, Konrad Krzewski
Published May 1, 2017
Citation Information: J Clin Invest. 2017;127(5):1905-1917. doi:10.1172/JCI89531.
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Categories: Research Article Immunology Inflammation

Dendritic cells expressing immunoreceptor CD300f are critical for controlling chronic gut inflammation

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.

Authors

Ha-Na Lee, Linjie Tian, Nicolas Bouladoux, Jacquice Davis, Mariam Quinones, Yasmine Belkaid, John E. Coligan, Konrad Krzewski

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CD300f deficiency leads to failure in resolution of colonic inflammation...

Figure 1

CD300f deficiency leads to failure in resolution of colonic inflammation.

(A–D) CD300f+/+ (CD300f WT) or CD300f–/– (CD300f KO) mice were given drinking water containing 2.5% DSS for 7 days, followed by unadulterated water for another 13 days (20 days total). “No DSS” indicates mice without DSS administration. DAI was scored during DSS administration, as described in Methods (A). On day 7 (Inflammation) and day 14 (Resolution), the colon length (B), macroscopic inflammation score (C), and microscopic inflammation score (D) were determined. The pictures in B–D are representative images from the indicated mice; note that CD300f–/– mice have shortened colons with loose stools (B), evident hyperemia (C), and destruction of colonic architecture with elevated cell infiltration (D). Scale bars in H&E staining images: 500 μm. Graphs show data quantification with means; error bars represent SEM (n = 3 in control, n = 15 in day 7, n = 15 in day 14). Two-tailed paired Student’s t test was used to determine statistical significance (*P < 0.05, **P < 0.01, ***P < 0.001).