Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Key Laboratory of Respiratory Diseases of National Health Commission of China, Wuhan, 430030, China.
Cell Commun Signal. 2024 Nov 19;22(1):554. doi: 10.1186/s12964-024-01911-4.
Interleukin-10 (IL-10), a pivotal anti-inflammatory cytokine, has gotten attention for its involvement in tissue remodeling and organ fibrosis. Pleurisy and subsequent pleural remodeling are recognized as quantifiable indicators of systemic lupus erythematosus (SLE) activity. However, the role of IL-10 in SLE-associated pleural remodeling remains unknown. In this study, we investigated role of IL-10 in SLE-associated pleural remodeling and the underlying mechanism.
Clinical data and serum specimens were obtained from SLE patients, while pleural mesothelial cells and mouse models served as primary experimental subjects. The protein expression-related technologies, histopathological staining, and other experimental methods were used in the study.
Our investigation got several key findings. Firstly, serum obtained from SLE patients with pleural thickening was found to induce pleural mesothelial cell remodeling. Subsequently, heightened levels of IL-10 were found in serum from SLE patients with pleural thickening compared to that of SLE patients without pleural thickening. Secondly, administration of recombinant IL-10 was confirmed its ability to induce pleural mesothelial cell remodeling, on the contrary, this remodeling was effectively mitigated by IL-10 inhibition. Notably, blockade of IL-10 significantly prevented collagen deposition and prevented thickening in pleura of SLE mouse models. Lastly, the IL-10/JAK2/STAT3/HIF1α/TMEM45A/P4HA1 signaling axis was elucidated to mediate pleural remodeling and thickening.
Our study uncovered that IL-10 mediated pleural remodeling in SLE. We suggested that serum IL-10 level exceeding 6.32 pg/mL was a potential reference threshold for predicting pleural thickening in SLE patients.
白细胞介素-10（IL-10）是一种关键的抗炎细胞因子，因其参与组织重塑和器官纤维化而受到关注。胸膜炎和随后的胸膜重塑被认为是系统性红斑狼疮（SLE）活动的可量化指标。然而，IL-10 在 SLE 相关的胸膜重塑中的作用尚不清楚。在这项研究中，我们研究了 IL-10 在 SLE 相关的胸膜重塑中的作用及其潜在机制。
从 SLE 患者中获取临床数据和血清标本，同时将胸膜间皮细胞和小鼠模型作为主要实验对象。使用蛋白质表达相关技术、组织病理学染色和其他实验方法进行研究。
我们的研究有几个关键发现。首先，从胸膜增厚的 SLE 患者中获得的血清被发现可诱导胸膜间皮细胞重塑。随后，发现胸膜增厚的 SLE 患者血清中的 IL-10 水平高于无胸膜增厚的 SLE 患者。其次，给予重组 IL-10 可证实其诱导胸膜间皮细胞重塑的能力，相反，IL-10 抑制可有效减轻这种重塑。值得注意的是，阻断 IL-10 可显著防止胶原沉积并防止 SLE 小鼠模型胸膜增厚。最后，阐明了 IL-10/JAK2/STAT3/HIF1α/TMEM45A/P4HA1 信号轴介导胸膜重塑和增厚。
我们的研究揭示了 IL-10 在 SLE 中介导的胸膜重塑。我们建议血清 IL-10 水平超过 6.32pg/mL 可能是预测 SLE 患者胸膜增厚的潜在参考阈值。
