title: Manifestation of spontaneous and early autoimmune gastritis in CCR7-deficient mice.
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 α 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.
authors.affiliation: Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Winter
authors.forename: Armin
authors.initials: A
authors.lastname: Rehm
authors.forename: Katharina
authors.initials: K
authors.lastname: Wichner
authors.forename: Tobias
authors.initials: T
authors.lastname: Scheel
authors.forename: Arvind
authors.initials: A
authors.lastname: Batra
authors.forename: Britta
authors.initials: B
authors.lastname: Siegmund
authors.forename: Claudia
authors.initials: C
authors.lastname: Berek
authors.forename: Martin
authors.initials: M
authors.lastname: Lipp
authors.forename: Uta E
authors.initials: UE
authors.lastname: Höpken
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology*; D001854:Bone Marrow Cells / Q000166:cytology; D039521:CD11c Antigen / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D003713:Dendritic Cells / Q000166:cytology; D005434:Flow Cytometry / Q000379:methods; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000473:pathology*; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000737:chemistry; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054400:Receptors, CCR7 / Q000235:genetics*
chemical_list: D039521:CD11c Antigen; C515371:Ccr7 protein, mouse; D007074:Immunoglobulin G; D020381:Interleukin-17; D054400:Receptors, CCR7; D007371:Interferon-gamma