Activation of Fibroblasts by Plasma Cells Via PDGF/PDGFR Signaling in IgG4-related Sialadenitis

Overview

Journal J Clin Exp Hematop

Specialties Hematology
Pathology

Date 2024 Sep 29

PMID 39343610

Authors

Takumi Kitaoka

Rintaro Ohe

Takanobu Kabasawa

Masayuki Kaneko

Nobuyuki Sasahara

Michihisa Kono

Kazushi Suzuki

Naoya Uchiyama

Rinako Ogawa

Mitsuru Futakuchi

Affiliations

Soon will be listed here.

Abstract

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.

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