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玉屏风配方对原发性干燥综合征的免疫调节作用:探究T细胞反应

Immunomodulatory effects of Yu-Ping-Feng formula on primary Sjögren syndrome: interrogating the T-cell response.

作者信息

Yu Sulan, Zhou Xinyao, Liu Ruihua, Xu Xiaoyu, Ma Danbao, Feng Yun, Lin Xiang

机构信息

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hon Kong SAR 999077, China.

Department of Rheumatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijng 100053, China.

出版信息

J Leukoc Biol. 2025 Feb 13;117(2). doi: 10.1093/jleuko/qiae155.

Abstract

Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, the underlying mechanism of immunomodulatory effects remains challenging, given the complicate composition of herbal medicines. Here, we developed an immunological approach to interrogate the T helper cell response. Through data mining, we hypothesized that Chinese medicine formula Yu-Ping-Feng might be a promising candidate for treating primary Sjögren syndrome, a common autoimmune disease manifested by exocrine gland dysfunction. We took advantage of a mouse model of experimental Sjögren syndrome that we previously established for Yu-Ping-Feng formula treatment. Yu-Ping-Feng therapy ameliorated the experimental Sjögren syndrome pathology in mice with active disease, showing improved salivary function and decreased serum levels of autoantibodies. Phenotypic analysis suggested that both effector T and B cells were significantly suppressed. Using coculture assay and adoptive transfer models, we demonstrated that Yu-Ping-Feng formula directly restrained effector/memory T-cell expansion and differentiation into Th17 and T follicular helper cells, the key subsets in experimental Sjögren syndrome pathogenesis. Importantly, we recruited 20 patients with primary Sjögren syndrome and conducted a pilot study of 8-wk therapy of Yu-Ping-Feng formula. Yu-Ping-Feng treatment effectively improved fatigue symptoms and exocrine gland functions, as well as reduced serum IgG/IgA levels, while effector T- and B-cell subsets were significantly decreased. There was a trend of reduction on disease activity, but not statistically significant. Together, our findings suggest a novel approach to assess the immunomodulatory effects of Yu-Ping-Feng formula, which may be favorable for patients with autoimmune disorders.

摘要

民族药理学治疗在自身免疫性疾病的临床实践中已显示出有益效果。然而,鉴于草药成分复杂,其免疫调节作用的潜在机制仍具有挑战性。在此,我们开发了一种免疫学方法来探究辅助性T细胞反应。通过数据挖掘,我们推测中药方剂玉屏风可能是治疗原发性干燥综合征的一个有前景的候选药物,原发性干燥综合征是一种以外分泌腺功能障碍为特征的常见自身免疫性疾病。我们利用先前建立的用于玉屏风方剂治疗的实验性干燥综合征小鼠模型。玉屏风治疗改善了患有活动性疾病的小鼠的实验性干燥综合征病理,唾液功能得到改善,自身抗体血清水平降低。表型分析表明效应性T细胞和B细胞均受到显著抑制。使用共培养试验和过继转移模型,我们证明玉屏风方剂直接抑制效应性/记忆性T细胞的扩增以及向Th17和滤泡辅助性T细胞的分化,这两种细胞是实验性干燥综合征发病机制中的关键亚群。重要的是,我们招募了20名原发性干燥综合征患者,并对玉屏风方剂进行了为期8周的治疗的初步研究。玉屏风治疗有效改善了疲劳症状和外分泌腺功能,同时降低了血清IgG/IgA水平,而效应性T细胞和B细胞亚群显著减少。疾病活动度有下降趋势,但无统计学意义。总之,我们的研究结果提示了一种评估玉屏风方剂免疫调节作用的新方法,这可能对自身免疫性疾病患者有益。

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