TNFΔARE Mice Display Abnormal Lymphatics and Develop Tertiary Lymphoid Organs in the Mesentery.
Chronic inflammatory diseases are associated with a persistent and enhanced response to environmental antigens. As an adaptive response to this exaggerated immune state, affected tissue typically develops tertiary lymphoid organs. Studies of Crohn disease (CD), a chronic inflammatory disease of the intestinal tract, report tertiary lymphoid organs present within the mucosal wall, along with other lymphatic diseases, such as lymphangiogenesis and obstructed lymphatic vessels. These observations suggest that downstream mesenteric lymphatic vessels and lymph drainage into mesenteric lymph nodes may be compromised. However, information is lacking on the morphologic features and functional status of mesenteric lymphatics in CD. Using confocal imaging, PCR, flow cytometry, and functional strategies, we addressed these questions in the established TNFΔARE mouse model of CD and found that this mouse model had many lymphatic abnormalities reminiscent of human CD. These abnormalities include intestinal lymphangiectasia, mesenteric lymph node lymphadenopathy, and lymphangiogenesis in both the mesentery and mucosa. Critically, TNFΔARE mice also present mesenteric tertiary lymphoid organs and have altered lymphatic transport of dendritic cells to mesenteric lymph nodes, two features likely to actively modulate immunity. Our findings provide key insights into lymphatic remodeling in the TNFΔARE mouse model. They shed light on the involvement of these lymphatic changes in immune dysfunctions observed in CD and suggest the lymphatic system as new target for therapeutic options.
Inflammation Research Network and Smooth Muscle Research Group, Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Sonia
S
Rehal
Inflammation Research Network and Smooth Muscle Research Group, Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address: vonderwe@ucalgary.ca.
Pierre-Yves
PY
von der Weid
D000818:Animals; D001692:Biological Transport; D000073883:CX3C Chemokine Receptor 1; D002908:Chronic Disease; D003713:Dendritic Cells / Q000378:metabolism; D007079:Ileitis / Q000473:pathology; D007082:Ileum / Q000473:pathology; D050356:Lipid Metabolism; D008198:Lymph Nodes / Q000473:pathology*; D000072281:Lymphadenopathy / Q000473:pathology; D042583:Lymphangiogenesis; D008208:Lymphatic System / Q000002:abnormalities* / Q000473:pathology*; D008643:Mesentery / Q000473:pathology*; D008822:Mice, Transgenic; D054400:Receptors, CCR7 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism
D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D054400:Receptors, CCR7; D019707:Receptors, Chemokine