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    Defective Lymphatics in Crohn’s Disease: Tertiary Lymphoid Follicles Plug the Gap

    McNamee, Eóin N. and Rivera-Nieves, Jesus (2017) Defective Lymphatics in Crohn’s Disease: Tertiary Lymphoid Follicles Plug the Gap. Gastroenterology, 152 (4). pp. 908-910. ISSN 0016-5085

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    The gut-associated lymphoid tissues are the guardians of the enteric immune system and integrate dietary and microbial stimuli to maintain immunologic tolerance. However, during periods of persistent chronic inflammation, such as in Crohn’s disease (CD), a dysfunctional lymphatic system is a pathologic hallmark. Indeed, the predominant histopathologic features of CD are lymphocytic lymphangitis, occluded lymphatic vessels, and inflammatory granulomas. These trademark features of chronic disease are found in or around ectopic tertiary lymphoid tissues (TLT) in the inflamed lamina propria (Gut 2008;57:1-4). In addition, the presence of TLT at the base of aphthous ulcers is the earliest endoscopically evident lesion in CD and their appearance heralds recurrent disease within the neoterminal ileum after ilectomy (Gut 1984;25:665-672). To date, the function of intestinal TLT and their impact on the etiology and pathogenesis of CD remains enigmatic, with limited experimental evidence as to their role. How TLT integrate into the pathophysiology of CD remains a critical question, yet clinical investigation into their development and function remains limited. Randolph et al aimed to assess the integrity of mesenteric lymphatic vasculature in CD. First, they confirmed the previous findings generated from immunopathologic studies of intestinal mucosa, indicating defective lymphatic function during active disease. To achieve this, patent blue dye was injected into the serosa of ileal loops before surgical resection, highlighting afferent lymphatic vessels draining the lamina propria. This technique nicely demonstrated a deviation of normal lymphatic vessels in active CD, compared with non-CD counterparts and indicated a remodeling of the vasculature in the mesentery. Next, they used a 3-dimensional system to image whole mount sections from a patient cohort undergoing ilectomy for stricturing CD (to obtain cm3 tissue coverage). Surprisingly, this work revealed advanced remodeling of the lymphatic vascular tracks, with the presence of ectopic lymphoid follicles within the collecting vessel line. A border of adipocytes and no evident capsule, suggesting that these organized structures were not sentinel lymph nodes but TLT instead. The work by Randolph et al highlights that, although most studies have reported on lymphatic capillaries in the intestinal wall, where collecting vessels remove solutes and immune cells, the primary functional site of lymphatic dysfunction may be the larger vessels in the mesentery, which interface with sentinel lymph nodes.

    Item Type: Article
    Keywords: Crohn’s disease (CD); lymphatic system; comment;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 11657
    Identification Number:
    Depositing User: Eoin McNamee
    Date Deposited: 12 Nov 2019 10:44
    Journal or Publication Title: Gastroenterology
    Publisher: Elsevier
    Refereed: Yes
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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