title: A mutant collagen XIII alters intestinal expression of immune response genes and predisposes transgenic mice to develop B-cell lymphomas.
abstract: Epithelial cells of mucosal surfaces are critical for maintaining immune homeostasis by aiding in the discrimination of pathogenic and commensal microorganisms and modulating the activities of antigen-presenting cells and lymphocytes. Functional breakdowns resulting in chronic infection and inflammation are associated with the development of hematologic and solid neoplasms for which detailed pathogenetic mechanisms are poorly understood. Mice heterozygous for a transgene Col13a1(del) expressing a mutant collagen XIII developed clonal mature B-cell lineage lymphomas originating in mesenteric lymph nodes (MLN). The tumors were associated with T cells and macrophages. The incidence of disease was reduced 2-fold in transgenic mice raised under specific pathogen-free conditions, suggesting a role for infectious agents. The lymphomas did not express the mutant collagen XIII, indicating that its influence on tumorigenesis was B-cell extrinsic and likely to be associated with collagen XIII-positive tissues drained by the MLN. Studies of the small intestines of transgenic mice showed that the subepithelial basement membranes (BM) were highly abnormal and that they exhibited heightened expression of genes involved in immune responses. These results define collagen XIII-dependent maintenance of the intestinal BM as a previously unappreciated component of immune responses and a critical determinant of cancer susceptibility.
authors.affiliation: Department of Medical Biochemistry, Oulu Center for Cell-Matrix Research, Institute of Biomedicine, University of Oulu, Oulu, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Tuomisto
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
authors.forename: Jenni
authors.initials: J
authors.lastname: Tahkola
authors.forename: Anne
authors.initials: A
authors.lastname: Latvanlehto
authors.forename: Eeva-Riitta
authors.initials: ER
authors.lastname: Savolainen
authors.forename: Helena
authors.initials: H
authors.lastname: Autio-Harmainen
authors.forename: Annikki
authors.initials: A
authors.lastname: Liakka
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.forename: Jussi
authors.initials: J
authors.lastname: Vuoristo
authors.forename: Anne
authors.initials: A
authors.lastname: West
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.forename: Taina
authors.initials: T
authors.lastname: Pihlajaniemi
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D024181:Collagen Type XIII / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D018928:Immunity, Mucosal / Q000235:genetics; D007421:Intestine, Small / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D024181:Collagen Type XIII