Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China.
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China.
Biomed Pharmacother. 2024 Aug;177:116885. doi: 10.1016/j.biopha.2024.116885. Epub 2024 Jun 15.
Sjögren's syndrome (SS) is an autoimmune disease in which the salivary glands (SGs) and the lacrimal glands (LGs) are affected by lymphocytic infiltration and inflammation. It has been reported that interferon-α (IFN-α) released by plasmacytoid dendritic cells (pDCs) contribute to the pathology of SS, and ART has been shown to effectively ameliorates SS. Despite the current research endeavors, the mechanism of how ART works in the treatment of SS remains to be fully elucidated. Whether ART can treat SS by inhibiting IFN-α remains unclear. This hypothesis was tested both in vivo and in vitro settings during the study. The SS model mice, which were treated with ART, showed amelioration in symptoms related to dryness. RNA-seq analysis revealed strong anti-IFN-α signaling response upon ART treatment. Additional in vitro studies provided further confirmation that the application of ART inhibits the MyD88 protein expression and the nuclear translocation of IRF7. This suggests that the intervention of ART in the TLR-MyD88-IRF7 pathway plays a role in the therapeutic approach for SS. In summary, this study highlighted the therapeutic potential of ART in SS and ART inhibited the IFN-α signaling in pDCs via the TLR-MyD88-IRF7 pathway.
干燥综合征（SS）是一种自身免疫性疾病，其特征为唾液腺（SGs）和泪腺（LGs）受到淋巴细胞浸润和炎症的影响。据报道，浆细胞样树突状细胞（pDCs）释放的干扰素-α（IFN-α）有助于 SS 的发病机制，而 ART 已被证明可有效改善 SS。尽管目前进行了大量研究，但 ART 治疗 SS 的机制仍未完全阐明。ART 是否可以通过抑制 IFN-α 来治疗 SS 尚不清楚。在这项研究中，我们在体内和体外环境中检验了这一假说。接受 ART 治疗的 SS 模型小鼠的干燥相关症状得到改善。RNA-seq 分析显示，ART 治疗后会出现强烈的抗 IFN-α 信号反应。此外，体外研究进一步证实，ART 的应用可抑制 MyD88 蛋白表达和 IRF7 的核转位。这表明，ART 干预 TLR-MyD88-IRF7 通路在 SS 的治疗方法中发挥作用。总之，本研究强调了 ART 在 SS 中的治疗潜力，ART 通过 TLR-MyD88-IRF7 通路抑制 pDCs 中的 IFN-α 信号。
