蛋白激酶 C-θ负反馈调节调节性 T 细胞功能。
Protein kinase C-theta mediates negative feedback on regulatory T cell function.
机构信息
Molecular Pathogenesis Program, Helen and Martin Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
出版信息
Science. 2010 Apr 16;328(5976):372-6. doi: 10.1126/science.1186068. Epub 2010 Mar 25.
Abstract
T cell receptor (TCR)-dependent regulatory T cell (Treg) activity controls effector T cell (Teff) function and is inhibited by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Protein kinase C-theta (PKC-theta) recruitment to the immunological synapse is required for full Teff activation. In contrast, PKC-theta was sequestered away from the Treg immunological synapse. Furthermore, PKC-theta blockade enhanced Treg function, demonstrating PKC-theta inhibits Treg-mediated suppression. Inhibition of PKC-theta protected Treg from inactivation by TNF-alpha, restored activity of defective Treg from rheumatoid arthritis patients, and enhanced protection of mice from inflammatory colitis. Treg freed of PKC-theta-mediated inhibition can function in the presence of inflammatory cytokines and thus have therapeutic potential in control of inflammatory diseases.
摘要
T 细胞受体 (TCR)-依赖性调节性 T 细胞 (Treg) 活性控制效应 T 细胞 (Teff) 的功能，并受到炎症细胞因子肿瘤坏死因子-α (TNF-α) 的抑制。蛋白激酶 C-θ (PKC-θ) 募集到免疫突触对于完全 Teff 激活是必需的。相比之下，PKC-θ 被隔离在 Treg 免疫突触之外。此外，PKC-θ 阻断增强了 Treg 的功能，表明 PKC-θ 抑制了 Treg 介导的抑制作用。PKC-θ 的抑制保护了 Treg 免受 TNF-α 的失活，恢复了类风湿关节炎患者缺陷 Treg 的活性，并增强了对小鼠炎症性结肠炎的保护作用。解除了 PKC-θ 介导的抑制作用的 Treg 可以在炎症细胞因子存在的情况下发挥作用，因此在控制炎症性疾病方面具有治疗潜力。
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