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易于诱导免疫耐受性,通过介质素-2-TGFβ代用激素

Qinli Sun¹, Alison K Barrett², Masato Ogishi¹

¹Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.

|March 12, 2026

概括

研究人员开发了一种新型IL-2-TGFβ联合激动剂,可在体内诱导调节性T细胞 (Treg细胞). 这种方法有效地抑制了过敏和自身免疫疾病模型中的免疫反应,提供了一个新的免疫治疗策略.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
治疗开发的治疗方法

背景情况:

CD4+调节性T细胞 (Treg细胞) 对于免疫耐受性至关重要.
周围诱导的Treg细胞 (pTreg细胞) 增强免疫反应调节.
现有的方法尚未充分利用IL-2和TGFβ用于免疫治疗中的体内pTreg细胞诱导.

研究的目的:

开发一种新型的协同激动剂,用于在体内诱导抗原特异性,功能性和稳定的pTreg细胞.
在炎症性,过敏性和自身免疫性疾病中研究这种协同激动剂的治疗潜力.

主要方法:

设计了一种单链融合蛋白,作为IL-2-TGFβ替代体的协同激动剂.
利用一个AND-gated机制,同时激活T细胞中的IL-2-STAT5和TGFβ-SMAD2/3信号.
在用卵蛋白 (OVA) 和髓寡细胞糖蛋白 (MOG) 免疫的小鼠模型中使用激素35-55.

主要成果:

在体内,IL-2-TGFβ替代体强烈诱导了抗原特异性,功能性和稳定的pTreg细胞.
诱导的pTreg细胞表现出具有高RORγt表达的效应器样状态,促进迁移和抑制炎症.
在过敏炎症和自身免疫神经炎症的小鼠模型中,治疗有效地改善了免疫激活.

结论:

开发的IL-2-TGFβ替代体共激动剂是诱导体内抗原特异性pTreg细胞的一个有前途的策略.
这种方法有可能在各种炎症,过敏和自身免疫疾病中建立免疫耐受性.
这些发现表明,针对免疫媒介疾病的免疫疗法有着新的治疗途径.

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