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针对拉巴胺复合体2的机械标减弱了系统性红斑狼的免疫病理

Minji Ai¹, Xian Zhou¹, Michele Carrer²

¹Division of Rheumatology, Department of Medicine, Mayo Clinic Rochester, MN, USA.

bioRxiv : the preprint server for biology

|August 12, 2024

概括

针对拉巴胺复合体 (mTORC) 2的机械性标显示出治疗系统性红斑狼 (SLE) 的前景. 抑制mTORC2在小鼠模型和人体细胞中减少了狼类症状,这表明SLE患者的新治疗途径.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
类风湿病学类风湿病学

背景情况:

系统性红斑狼 (SLE) 是一种复杂的自身免疫性疾病,治疗选择有限.
拉巴胺复合体 (mTORC) 2的机械标与免疫细胞功能和自身免疫有关.
I型干扰素 (IFN) 信号传输在SLE的发病过程中起着至关重要的作用.

研究的目的:

研究mTORC2在SLE发育中的作用.
探索在自身免疫中通过I型IFN信号调节mTORC2的作用.
为了评估mTORC2向治疗改善狼类症状.

主要方法:

在T细胞特异性Rictor缺陷小鼠中使用imiquimod诱导狼类疾病.
在I型IFNAR缺陷Lpr小鼠中评估mTORC2信号和免疫表型.
在MRL/lpr小鼠和人类PBMC中对抗Rictor反感小核酸 (Rictor-ASO) 的治疗性评估.

主要成果:

针对T细胞的Rictor缺陷减少了B细胞种群,自身抗体和在Imiquimod治疗后的疾病严重程度.
在Lpr小鼠中,IFNAR1缺乏导致mTORC2活性降低,T细胞代谢改善,炎症减少.
里克托-ASO治疗改善了MRL/lpr小鼠的功能和免疫病理,并减少了人类SLE PBMCs中的免疫球蛋白/自身抗体的产生.

结论:

针对mTORC2是一种潜在的SLE治疗策略.
mTORC2抑制在临床前狼模型和人体细胞中显示出有效性.
对mTORC2向性SLE治疗的进一步研究是有必要的.

关键词:

系统性红血性狼 (Systemic lupus erythematosusus) 是一种全身性狼.这是一种反意义的寡核酸.免疫病理学免疫病理学在 mTORC2 中,mTORC2 是指mTORC2.

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