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    Ectopic lymphoid tissue alters the chemokine gradient, increases lymphocyte retention and exacerbates murine ileitis


    McNamee, Eóin N. and Masterson, Joanne C. and Jedlicka, Paul and Collins, Colm B. and Williams, Ifor R. and Rivera-Nieves, Jesus (2013) Ectopic lymphoid tissue alters the chemokine gradient, increases lymphocyte retention and exacerbates murine ileitis. Gut, 62 (1). pp. 53-62. ISSN 1468-3288

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    Abstract

    Background The earliest endoscopically-evident lesion in Crohn’s disease is the aphthous ulcer, which develops over ectopic lymphoid tissues (ie, inducible lymphoid follicles (ILF), tertiary lymphoid tissue (TLT)) in the chronically inflamed intestine. ILF/TLT are induced within effector sites by homeostatic lymphoid chemokines, but their role in the development of intestinal ILF/TLT and in the pathogenesis of Crohn’s disease is poorly understood. Design Using a mouse model of Crohn’s-like ileitis (TNFΔARE) which develops florid induction of ILF/TLT within its terminal ileum, the contribution of the CCR7/ CCL19/CCL21 chemokine axis during the development of TLT and its role in disease pathogenesis were assessed. Results Both CCL19 and CCL21 were increased within the inflamed ileum of TNFΔARE mice, which resulted in CCR7 internalisation and impaired T cell chemotaxis. ILF/ TLT were a major source of CCL19 and CCL21 and increased local synthesis, augmented recruitment/ retention of effector, naı¨ve and central memory T cell subsets within the inflamed ileum. Immunoblockade of CCR7 resulted in further effector T cell retention and exacerbation of ileitis. Conclusions Induction of ILF/TLT in the chronically inflamed intestine alters the homeostatic CCL19-CCL21 lymphoid-chemokine gradient and increases recruitment/ retention of effector CCR7+ T cell subsets within the terminal ileum, contributing to the perpetuation of chronic inflammation. Thus, blockade of CCR7 or its ligands might result in deleterious consequences for subjects with chronic inflammatory diseases.

    Item Type: Article
    Keywords: Ectopic; lymphoid tissue; alters; chemokine gradient; increases lymphocyte retention; exacerbates; murine ileitis;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12489
    Identification Number: https://doi.org/10.1136/gutjnl-2011-301272
    Depositing User: Joanne Masterson
    Date Deposited: 27 Feb 2020 14:29
    Journal or Publication Title: Gut
    Publisher: BMJ Publishing Group
    Refereed: Yes
    URI:

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