Department of Medicine, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume, Japan.
Dental and Oral Medical Center, Kurume University School of Medicine, Kurume, Japan.
Mod Rheumatol. 2022 Jul 1;32(4):761-769. doi: 10.1093/mr/roab051.
This study investigated the associations of mast cells with immune-mediated inflammation and fibrosis in patients with primary Sjögren's syndrome (pSS); it also explored the underlying pathophysiology of pSS-related sialadenitis.
Twenty-two patients with pSS and 10 patients with sicca (control individuals) underwent labial salivary gland biopsies. Sections were subjected to staining and immunofluorescence analyses. HMC-1 human mast cells were cocultured with fibroblasts in vitro; fibroblasts were also grown in HMC-1 conditioned medium. mRNA levels of collagen Type I (Col1a) and transforming growth factor (TGF)β1 were analysed in cultured cells.
Mast cell numbers in labial salivary glands were significantly greater in patients with pSS than in control individuals. In salivary glands from patients with pSS, mast cell number was significantly correlated with fibrosis extent; moreover, mast cells were located near fibrous tissue and expressed TGFβ1. Col1a and TGFβ1 mRNAs were upregulated in cocultured fibroblasts and HMC-1 cells, respectively. Fibroblasts cultured in HMC-1 conditioned medium exhibited upregulation of Col1a mRNA; this was abrogated by TGFβ1 neutralizing antibodies.
Mast cell numbers were elevated in patients with pSS-related sialadenitis; these cells were located near fibroblasts and expressed TGFβ1. TGFβ1 could induce collagen synthesis in fibroblasts, which might contribute to fibrosis.
本研究旨在探讨肥大细胞与原发性干燥综合征（pSS）患者免疫介导的炎症和纤维化的关系；并探索 pSS 相关涎腺炎的潜在病理生理学机制。
对 22 例 pSS 患者和 10 例干燥综合征对照个体进行唇腺活检。对切片进行染色和免疫荧光分析。体外将 HMC-1 人肥大细胞与成纤维细胞共培养；并将成纤维细胞培养在 HMC-1 条件培养基中。分析培养细胞中Ⅰ型胶原（Col1a）和转化生长因子（TGF）β1 的 mRNA 水平。
pSS 患者唇腺中的肥大细胞数量明显多于对照组。在 pSS 患者的唾液腺中，肥大细胞数量与纤维化程度显著相关；此外，肥大细胞位于纤维组织附近，并表达 TGFβ1。共培养的成纤维细胞和 HMC-1 细胞中 Col1a 和 TGFβ1 的 mRNA 均上调。在 HMC-1 条件培养基中培养的成纤维细胞中 Col1a mRNA 上调；用 TGFβ1 中和抗体可阻断此上调。
pSS 相关涎腺炎患者的肥大细胞数量增加；这些细胞位于成纤维细胞附近并表达 TGFβ1。TGFβ1 可诱导成纤维细胞合成胶原，这可能导致纤维化。
