AS101调节Teff/Treg平衡,通过调节NFATc2来缓解子自身免疫性乳腺炎
Xiu Wang1, Na Li1, Jiawen Zhang1
1Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin China, China.
Experimental eye research
|May 23, 2024
概括
AS101有效地治疗了斯约格伦.
科学领域:
- 免疫学 免疫学 免疫学
- 眼科医生 眼科 眼科
- 药理学 药理学是指药理学的学科.
背景情况:
- 肖格伦综合征 (SS) 干眼导致眼睛炎症和眼腺损伤,治疗选择有限.
- 自免疫干眼模型对于了解疾病机制和评估治疗干眼的治疗干眼模型至关重要.
研究的目的:
- 为了研究AS101在自身免疫干眼中的治疗潜力.
- 阐明AS101的潜在免疫调节机制,重点关注T细胞平衡和NFATc2.2.
- 评估AS101对眼腺炎症和功能的影响.
主要方法:
- AS101是通过下注射在自身免疫性大腺炎的子模型中进行的.
- 进行了临床和组织学评估,以评估治疗效果.
- 定量实时PCR和西班牙布洛特分析了T细胞转录因子 (Teff/Treg),细胞因子,炎症媒介和NFATc2的基因和蛋白质表达 in vivo和 in vitro.
- 进一步探索了NFATc2的作用,使用外围血液淋巴细胞 (PBLs) 感染NFATc2过度表达的lentiviral等离子体.
主要成果:
- AS101显著降低了临床严重程度和眼腺炎症.
- AS101治疗降低了Th1和Th17相关基因表达,同时增加了调控性T细胞 (Treg) 相关基因Foxp3表达.
- AS101抑制了关键的炎症媒介,包括TNF-α,IL-1β,IL-23,IL-6,MMP-2和MMP-9.
- 在炎症的眼腺中,AS101降低了NFATc2的表达;NFATc2的过度表达部分抑制了AS101对T细胞的免疫调节作用.
结论:
- AS101在自身免疫干眼模型中显示出强大的治疗效果.
- AS101充当效应T细胞 (Teff) /Treg细胞平衡的潜在调节者.
- 通过调节NFATc2依赖性免疫反应,AS101代表了Sjögren综合征干眼的有希望的治疗药物.
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