title: CCAAT/enhancer binding protein α (C/EBPα)(+) M2 macrophages contribute to fibrosis in IgG4-related disease?
abstract: IgG4-related disease (IgG4-RD) is a new disease entity characterized by type 2 helper T (Th2)-dominant inflammation and progressive fibrosis. We found the infiltration of strange cell populations in the fibrotic lesions of submandibular gland specimens obtained from 15 patients with IgG4-RD. These cells expressed CCAAT/enhancer binding protein a (C/EBPα). Many of the cell populations were identified with M2 macrophages. The degrees of infiltration of C/EBPα(+)M2 macrophages and the ratio of fibrotic lesions in the specimens were correlated (r(2) = 0.83, p < 0.01). We also analyzed the expression of C/EBPα in other chronic inflammatory disorders: synovium in rheumatoid arthritis (RA), liver tissue in chronic viral hepatitis, and mucosa in ulcerative colitis. The specimens from RA and chronic viral hepatitis showed infiltration of C/EBPα(+) cells, but there were few C/EBPα-positive cells in ulcerative colitis. Fibrosis is not a major issue in ulcerative colitis. In conclusion, we found the remarkable infiltration of C/EBPα(+)M2 macrophages in cases of chronic inflammation with fibrosis, including IgG4-RD. This primitive study also disclosed that most of C/EBPα(+)M2 macrophages localized in fibrotic lesions, and the degree of the infiltration and the ratio of fibrotic area were correlated.
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine , Sapporo , Japan.
authors.forename: Motohisa
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Yui
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yajima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishigami
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tabeya
authors.forename: Chisako
authors.initials: C
authors.lastname: Suzuki
authors.forename: Mikiko
authors.initials: M
authors.lastname: Matsui
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Naishiro
authors.forename: Kohzon
authors.initials: K
authors.lastname: Imai
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Shinomura
mesh_terms: D000368:Aged; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D005260:Female; D005355:Fibrosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013363:Submandibular Gland / Q000378:metabolism / Q000473:pathology
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D007074:Immunoglobulin G
keywords: CCAAT/enhancer binding protein α; Fibrosis; IgG4-related disease; Macrophage