title: Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease.
abstract: Early pathological descriptions of Crohn disease (CD) argued for a potential defect in lymph transport; however, this concept has not been thoroughly investigated. In mice, poor healing in response to infection-induced tissue damage can cause hyperpermeable lymphatic collecting vessels in mesenteric adipose tissue that impair antigen and immune cell access to mesenteric lymph nodes (LNs), which normally sustain appropriate immunity. To investigate whether analogous changes might occur in human intestinal disease, we established a three-dimensional imaging approach to characterize the lymphatic vasculature in mesenteric tissue from controls or patients with CD. In CD specimens, B-cell-rich aggregates resembling tertiary lymphoid organs (TLOs) impinged on lymphatic collecting vessels that enter and exit LNs. In areas of creeping fat, which characterizes inflammation-affected areas of the bowel in CD, we observed B cells and apparent innate lymphoid cells that had invaded the lymphatic vessel wall, suggesting these cells may be mediators of lymphatic remodeling. Although TLOs have been described in many chronic inflammatory states, their anatomical relationship to preestablished LNs has never been revealed. Our data indicate that, at least in the CD-affected mesentery, TLOs are positioned along collecting lymphatic vessels in a manner expected to affect delivery of lymph to LNs.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: grandolph@path.wustl.edu.
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Shashi
authors.initials: S
authors.lastname: Bala
authors.affiliation: Department of Gastroenterology and Hepatology, Central University Hospital Catholic University of Louvain Namur, Yvoir, Belgium.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rahier
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Johnson
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Wang
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: ILKe
authors.initials: I
authors.lastname: Nalbantoglu
authors.affiliation: UMR995-LIRIC, INSERM, University of Lille, Lille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Dubuquoy
authors.affiliation: Department of Surgery, Centre Hospitalier Régional Universitaire (CHRU), Lille University North of France, Lille, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Chau
authors.affiliation: Department of Hepatology and Gastroenterology, Centre Hospitalier Régional Universitaire (CHRU), Lille University North of France, Lille, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pariente
authors.affiliation: Colorectal Surgery Unit, University Clinic of St-Luc, Catholic University of Louvain, Brussels, Belgium.
authors.forename: Alex
authors.initials: A
authors.lastname: Kartheuser
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Zinselmeyer
authors.affiliation: Division of Gastroenterology, Department of Medicine, Icahn Medical School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
mesh_terms: D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D003424:Crohn Disease / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007082:Ileum / Q000000981:diagnostic imaging / Q000473:pathology; D021621:Imaging, Three-Dimensional; D007249:Inflammation; D007422:Intestines / Q000473:pathology / Q000601:surgery; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D042601:Lymphatic Vessels / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D008297:Male; D008643:Mesentery / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D051379:Mice; D008875:Middle Aged; D000072717:Tertiary Lymphoid Structures / Q000000981:diagnostic imaging / Q000473:pathology