Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
PLoS One. 2023 Aug 2;18(8):e0281881. doi: 10.1371/journal.pone.0281881. eCollection 2023.
Enhanced circulating blood periostin levels positively correlate with disease severity in patients with systemic sclerosis (SSc). Monocytes/macrophages are predominantly associated with the pathogenesis of SSc, but the effect of periostin on immune cells, particularly monocytes and macrophages, still remains to be elucidated. We examined the effect of periostin on monocytes and monocyte-derived macrophages (MDM) in the pathogenesis of SSc. The modified Rodnan total skin thickness score in patients with dcSSc was positively correlated with the proportion of CD80-CD206+ M2 cells. The proportion of M2 macrophages was significantly reduced in rPn-stimulated MDMs of HCs compared to that of SSc patients. The mRNA expression of pro-fibrotic cytokines, chemokines, and ECM proteins was significantly upregulated in rPn-stimulated monocytes and MDMs as compared to that of control monocytes and MDMs. A similar trend was observed for protein expression in the respective MDMs. In addition, the ratio of migrated cells was significantly higher in rPn-stimulated as compared to control monocytes. These results suggest that periostin promotes inflammation and fibrosis in the pathogenesis of SSc by possible modulation of monocytes/macrophages.
在系统性硬化症(SSc)患者中,循环血液骨膜蛋白水平升高与疾病严重程度呈正相关。单核细胞/巨噬细胞主要与 SSc 的发病机制相关,但骨膜蛋白对免疫细胞,特别是单核细胞和巨噬细胞的影响仍有待阐明。我们研究了骨膜蛋白对 SSc 发病机制中单核细胞和单核细胞衍生的巨噬细胞(MDM)的影响。dcSSc 患者的改良 Rodnan 总皮肤厚度评分与 CD80-CD206+ M2 细胞的比例呈正相关。与 SSc 患者相比,HC 中 rPn 刺激的 MDM 中 M2 巨噬细胞的比例明显降低。与对照单核细胞和 MDM 相比,rPn 刺激的单核细胞和 MDM 中促纤维化细胞因子、趋化因子和 ECM 蛋白的 mRNA 表达显著上调。相应的 MDM 中也观察到了类似的蛋白表达趋势。此外,rPn 刺激的迁移细胞比例明显高于对照单核细胞。这些结果表明,骨膜蛋白可能通过调节单核细胞/巨噬细胞促进 SSc 的炎症和纤维化发病机制。