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用合成托芬代谢物治疗自身免疫性神经炎症的治疗方法

Michael Platten¹, Peggy P Ho, Sawsan Youssef

¹Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA. michael.platten@uni-tuebingen.de

Science (New York, N.Y.)

|November 8, 2005

概括

氨酸2,3-二氧化酶 (IDO) 通过分解氨酸来调节T细胞免疫力. 它的代谢物抑制T细胞,为治疗多发性硬化症 (MS) 等自身免疫性疾病提供了新的策略.

科学领域:

免疫学免疫学免疫学
神经科学是一个神经科学.
药理学药理学是指药理学的学科.

背景情况:

氨酸 (Trp) 通过氨酸二,三氧化酶 (IDO) 的局部代谢是T细胞介导免疫的关键调节者.
IDO在免疫耐受性中起着至关重要的作用,并与各种自身免疫性疾病有关.

研究的目的:

调查IDO和托催化剂在与自身免疫疾病相关的T细胞反应中的作用.
评估IDO途径调制在实验性自身免疫脑膜炎 (EAE) 的治疗潜力,多发性硬化症 (MS) 的模型.

主要方法:

用可容纳的改变自我激活髓特异性T细胞.
分析了氨酸2,3-二氧化酶 (IDO) 转录水平.
评估托芬催化剂对T细胞增殖和细胞因子产生的影响.
实验性自身免疫脑膜炎 (EAE) 小鼠的治疗与N-(3,4,-Dimethoxycinnamoyl) 人类酸 (3,4-DAA).

主要成果:

在用宽容性激素刺激髓特异性T细胞时,IDO转录增加.
托芬催化剂抑制了髓特异性的T细胞增殖,并抑制了T辅助-1 (T(H) 1) 细胞因子的产生.
合成衍生物3,4-DAA在患有EAE的小鼠中逆转了.

结论:

通过IDO介导的托芬代谢是调节T细胞免疫力的重要机制.
托芬催化剂及其合成衍生物显示出对T(H) 1介导的自身免疫性疾病的治疗潜力.
这一途径为治疗多发性硬化症 (MS) 等疾病提供了一种新的策略.

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