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Transition from an autoimmune-prone state to fatal autoimmune disease in CCR7 and RORγt double-deficient mice is dependent on gut microbiota

Item Type:Article
Title:Transition from an autoimmune-prone state to fatal autoimmune disease in CCR7 and RORγt double-deficient mice is dependent on gut microbiota
Creators Name:Wichner, K. and Fischer, A. and Winter, S. and Tetzlaff, S. and Heimesaat, M.M. and Bereswill, S. and Rehm, A. and Lipp, M. and Höpken, U.E.
Abstract:Autoimmunity is associated with a strong genetic component, but onset and persistence of clinically apparent autoimmune diseases often require an additional environmental trigger. The balance between immunity and tolerance is regulated by numerous molecular factors including nuclear hormone and homeostatic chemokine receptors. The nuclear hormone receptor ROR{gamma}t and the chemokine receptor CCR7 are both essentially involved in functional lymphoid organogenesis and maintenance of lymphocyte homeostasis. Lack of one or the other impairs thymic T cell development and alters T cell homeostasis. Mice deficient for both, Ccr7-/-Ror{gamma}t-/-, succumbed early to acute destructive inflammation, characterized by massive recruitment of inflammatory leukocytes, pro-inflammatory cytokine and autoantibody production, and wasting disease. Antibiotic-treatment of mice before disease onset reduced the overall gut microflora and abrogated the development of fatal mucosal inflammation. Hence, commensal bacteria and a confined tissue-specific inflammatory milieu serve as complementary trigger to initiate the lethal pathophysiologic process in Ccr7-/-Ror{gamma}t-/- mice.
Keywords:Homeostatic Chemokine Receptor, Retinoic Acid Receptor-Related Orphan Receptor, Thymic T Cell Development, Mucosal Inflammation, Gut Microbiota, Animals, Mice
Source:Journal of Autoimmunity
ISSN:0896-8411
Publisher:Elsevier / Academic Press (U.K.)
Volume:47
Page Range:58-72
Date:December 2013
Official Publication:https://doi.org/10.1016/j.jaut.2013.08.007
PubMed:View item in PubMed

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