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Divergent Roles for Macrophage C-Type Lectin Receptors, Dectin-1 and Mannose Receptors, in Inflammatory Bowel Diseases

46 Pages Posted: 9 Jun 2019 Publication Status: Published

See all articles by Mouna Rahabi

Mouna Rahabi

Université de Toulouse - UMR 152 Pharma Dev

Godefroy Jacquemin

Université de Toulouse - UMR 152 Pharma Dev

Mélissa Prat

Université de Toulouse - UMR 152 Pharma Dev

Etienne Meunier

University of Toulouse - Institute of Pharmacology and Structural Biology (IPBS); Université de Toulouse - UMR 152 Pharma Dev

Mohamad AlaEddine

Université de Toulouse - UMR 152 Pharma Dev

Bénédicte Bertrand

Université de Toulouse - UMR 152 Pharma Dev

Lise Lefèvre

Université de Toulouse - UMR 152 Pharma Dev

Khaddouj Benmoussa

Université de Toulouse - UMR 152 Pharma Dev

Philippe Batigne

Université de Toulouse - UMR 152 Pharma Dev

Agnès Aubouy

Université de Toulouse - UMR 152 Pharma Dev

Johan Auwerx

École Polytechnique Fédérale de Lausanne - Laboratory of Integrative Systems Physiology

Sylvain Kirzin

Université de Toulouse, CHU Purpan, Department of Surgery and Digestive Diseases

Delphine Bonnet

Université de Toulouse, CHU Purpan, Department of Internal Medicine and Digestive Diseases

Marie Danjoux

Université de Toulouse, CHU Purpan, Department of Pathology

Bernard Pipy

Université de Toulouse - UMR 152 Pharma Dev

Laurent Alric

Université de Toulouse - UMR 152 Pharma Dev

Agnès Coste

Université de Toulouse - UMR 152 Pharma Dev

Hélène Authier

Université de Toulouse - UMR 152 Pharma Dev

More...

Abstract

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.

Keywords: C-type lectin receptors, colitis, mucosal immunity, innate immune response, mannose receptor, Dectin-1, Macrophage

Suggested Citation

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.

Mouna Rahabi

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Godefroy Jacquemin

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Mélissa Prat

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Etienne Meunier

University of Toulouse - Institute of Pharmacology and Structural Biology (IPBS) ( email )

205 Route de Narbonne
31400
United States

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Mohamad AlaEddine

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Bénédicte Bertrand

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Lise Lefèvre

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Khaddouj Benmoussa

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Philippe Batigne

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Agnès Aubouy

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Johan Auwerx

École Polytechnique Fédérale de Lausanne - Laboratory of Integrative Systems Physiology ( email )

Lausanne
Switzerland

Sylvain Kirzin

Université de Toulouse, CHU Purpan, Department of Surgery and Digestive Diseases ( email )

France

Delphine Bonnet

Université de Toulouse, CHU Purpan, Department of Internal Medicine and Digestive Diseases ( email )

France

Marie Danjoux

Université de Toulouse, CHU Purpan, Department of Pathology ( email )

France

Bernard Pipy

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Laurent Alric

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Agnès Coste

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

Hélène Authier (Contact Author)

Université de Toulouse - UMR 152 Pharma Dev ( email )

France

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