Autor: |
Kitaoka T; Department of Pathology, Yamagata University Faculty of Medicine, Yamagata, Japan., Ohe R; Department of Pathology, Yamagata University Faculty of Medicine, Yamagata, Japan., Kabasawa T; Department of Pathology, Yamagata University Faculty of Medicine, Yamagata, Japan., Kaneko M; Department of Pathology, Yamagata University Faculty of Medicine, Yamagata, Japan.; Department of Otolaryngology, Head and Neck Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan., Sasahara N; Department of Pathology, Yamagata University Faculty of Medicine, Yamagata, Japan.; Department of Dentistry, Oral and Maxillofacial·Plastic and Reconstructive Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan., Kono M; Department of Pathology, Yamagata University Faculty of Medicine, Yamagata, Japan., Suzuki K; Department of Pathology, Yamagata University Faculty of Medicine, Yamagata, Japan., Uchiyama N; Department of Pathology, Yamagata University Faculty of Medicine, Yamagata, Japan., Ogawa R; Department of Pathology, Yamagata University Faculty of Medicine, Yamagata, Japan., Futakuchi M; Department of Pathology, Yamagata University Faculty of Medicine, Yamagata, Japan. |
Abstrakt: |
IgG4-related sialadenitis (IgG4-SA) is one of the IgG4-related disease. The histological features of IgG4-SA include dense lymphoplasmacytic infiltrates and fibrosis. This study aimed to reveal the involvement of plasma cells in the development of fibrosis and the mechanism underlying fibrosis in IgG4-SA. Hematoxylin-eosin staining, Azan staining, silver staining, and immunohistochemistry (IHC) were performed on IgG4-SA and chronic sialadenitis specimens, and theses samples were analyzed by image analysis software. Histological spatial analysis was used to analyze the localization of IHC-positive cells and the distances between these cells. In the IgG4-SA group, many secondary lymphoid follicles with germinal centers were found, and many collagen fibers developed around these germinal centers. Collagen fibers composed mainly of type I collagen was abundant at sites away from secondary lymphoid follicles, and reticular fibers composed of type III collagen was abundant near secondary lymphoid follicles. Many FAP + fibroblasts and MUM1 + plasma cells were localized near secondary lymphoid follicles. Histological spatial analysis demonstrated that 90.4% of MUM1 + plasma cells accumulated within 20 µm of FAP + fibroblasts. Multiple immunofluorescence assays revealed that MUM1 + plasma cells expressed platelet-derived growth factor (PDGF) β, and FAP + fibroblasts expressed PDGF receptor (PDGFR) β and pSTAT3 in IgG4-SA. We have shown that fibrosis is localized around secondary lymphoid follicles and that fibroblasts are activated by plasma cells via PDGF/PDGFR signaling in IgG4-SA. |