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 April 17, 2017
Citation Information: J Clin Invest. 2017;127(5):1905-1917. https://doi.org/10.1172/JCI89531.
View: Text | PDF
Research Article Immunology Inflammation Article has an altmetric score of 2

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

×

Figure 2

CD300f deficiency leads to sustained and elevated TNF-α production, which is responsible for induction of other proinflammatory cytokines and exacerbation of colonic inflammation.

Options: View larger image (or click on image) Download as PowerPoint
CD300f deficiency leads to sustained and elevated TNF-α production, whic...
(A) Mice were treated as indicated in Figure 1A. Cytokine levels in the colon tissues of CD300f+/+ and CD300f–/– mice were determined on day 7 (Inflammation) and day 14 (Resolution). (B) Colon sections from CD300f+/+ and CD300f–/– mice, collected on day 7 (Inflammation) or day 14 (Resolution), were stained for TNF-α or IFN-γ (left panels); scale bars: 20 μm. The fluorescence signal intensity was determined for each image (middle panels) and plotted as 3D surface plots (right panels). (C–G) Infliximab or PBS (vehicle) was injected i.v. to CD300f+/+ or CD300f–/– mice every other day during 2.5% DSS treatment, and every 3 days during the following 5 days. DAI was scored during and after DSS administration; infliximab injection times are indicated (C). On day 12, the colon length (D), macroscopic inflammation score (E), and microscopic inflammation score (F) were determined. The images in F illustrate representative results of H&E staining of the colon tissues from CD300f–/– mice; scale bars: 500 μm. (G) Levels of the indicated cytokines in colon tissue lysates from CD300f+/+ and CD300f–/– mice. All graphs show mean values ± SEM (n = 5, each group). Two-tailed paired Student’s t test was used to determine statistical significance (*P < 0.05, **P < 0.01).