Colonic macrophages are considered as major effectors of inflammatory bowel diseases (IBD), and the control of gut inflammation through C-type lectin receptors is an emerging concept. We show that during colitis the loss of Dectin-1 prevents intestinal inflammation, while the lack of MR exacerbates it. A marked increase in Dectin-1 expression in DSS-exposed MR-deficient mice, support the critical contribution of Dectin-1 in the development of colitis. Dectin-1 is crucial for Ly6ChighCCR2high monocyte population enrichment in the blood and their recruitment to inflamed colon as precursors of M1 inflammatory macrophages. Dectin-1 also promotes inflammasome-dependent IL-1β secretion through the leukotriene B4 production. Interestingly, the colonic inflammation is associated with a concomitant overexpression of Dectin-1/CCL2/LTA4H and a down-regulation of MR on macrophages from IBD patients. Thus, MR and Dectin-1 on macrophage are important mucosal inflammatory regulators during IBD. Finally, this study offers breakthroughs on the mechanism may contribute to the pathogenesis of IBD in humans.
Rahabi, Mouna and Jacquemin, Godefroy and Prat, Mélissa and Meunier, Etienne and AlaEddine, Mohamad and Bertrand, Bénédicte and Lefèvre, Lise and Benmoussa, Khaddouj and Batigne, Philippe and Aubouy, Agnès and Auwerx, Johan and Kirzin, Sylvain and Bonnet, Delphine and Danjoux, Marie and Pipy, Bernard and Alric, Laurent and Coste, Agnès and Authier, Hélène, Divergent Roles for Macrophage C-Type Lectin Receptors, Dectin-1 and Mannose Receptors, in Inflammatory Bowel Diseases (June 7, 2019). Available at SSRN: https://ssrn.com/abstract=3400857 or http://dx.doi.org/10.2139/ssrn.3400857
This version of the paper has not been formally peer reviewed.
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