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Manifestation of spontaneous and early autoimmune gastritis in CCR7-deficient mice

Item Type:Article
Title:Manifestation of spontaneous and early autoimmune gastritis in CCR7-deficient mice
Creators Name:Winter, S. and Rehm, A. and Wichner, K. and Scheel, T. and Batra, A. and Siegmund, B. and Berek, C. and Lipp, M. and Hoepken, U.E.
Abstract:Autoimmune gastritis is a common autoimmune disorder characterized by chronic inflammatory cell infiltrates, atrophy of the corpus and fundus, and the occurrence of autoantibodies to parietal cell antigen. In CCR7-deficient mice, autoimmune gastritis developed spontaneously and was accompanied by metaplasia of the gastric mucosa and by the formation of tertiary lymphoid organs at gastric mucosal sites. T cells of CCR7-deficient mice showed an activated phenotype in the gastric mucosa, mesenteric lymph nodes, and peripheral blood. In addition, elevated serum IgG levels specific to gastric parietal cell antigen were detected. Because the role of organized lymphocytic aggregates at this inflammatory site is not completely understood, we first analyzed the cellular requirements for the formation of these structures. Autoreactive CD4(+) T cells were pivotal for tertiary lymphoid follicle formation, most likely in cooperation with dendritic cells, macrophages, and B cells. Second, we analyzed the necessity of secondary lymph nodes and tertiary lymphoid organs for the development of autoimmune gastritis using CCR7 single- and CCR7/lymphotoxin alpha double-deficient mice. Strikingly, manifestation of autoimmune gastritis was observed in the absence of secondary lymph nodes and preceded the development of tertiary lymphoid organs. Taken together, these findings identify an inflammatory process where gastric autoreactive T cells independent of organized tertiary lymphoid organs and classic lymph nodes can induce and maintain autoimmune gastritis.
Keywords:Autoimmune Diseases, Bone Marrow Cells, CCR7 Receptors, CD11c Antigens, CD4-Positive T-Lymphocytes, Dendritic Cells, Flow Cytometry, Gastritis, Hydrogen-Ion Concentration, Immunoglobulin G, Inbred C57BL Mice, Interferon-gamma, Interleukin-17, Mononuclear Leukocytes, Stomach, Transgenic Mice, Animals, Mice
Source:American Journal of Pathology
ISSN:0002-9440
Publisher:Elsevier (U.S.A.)
Volume:179
Number:2
Page Range:754-765
Date:August 2011
Official Publication:https://doi.org/10.1016/j.ajpath.2011.04.012
PubMed:View item in PubMed

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