Dopamine, through the extracellular signal-regulated kinase pathway, downregulates CD4+CD25+ regulatory T-cell activity:: Implications for neurodegeneration
Dopamine, through the extracellular signal-regulated kinase pathway, downregulates CD4+CD25+ regulatory T-cell activity:: Implications for neurodegeneration
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DOI：
10.1523/jneurosci.0600-04.2004
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发表时间：
2004-07-07
影响因子：
5.3
通讯作者：
Schwartz, M
中科院分区：
文献类型：
--
作者：
Kipnis, J;Cardon, M;Schwartz, M
对抗神经元变性需要对中枢神经系统损伤部位的自身抗原进行良好控制的 T 细胞反应。引起这种反应的能力通常受到天然存在的 CD4(+) CD25(+) 调节性 T 细胞 (Treg) 的抑制。尚未鉴定出控制 Treg 活性的生理化合物。在这里，我们证明多巴胺通过 1 型多巴胺受体（此处发现 Treg 优先表达）发挥作用，降低 Treg 的抑制活性以及粘附和迁移能力。 Treg 活性与 ERK1/2（细胞外信号调节激酶 1/2）信号通路的激活相关。全身注射多巴胺或其 1 型受体激动剂，通过 T 细胞依赖性机制，显着增强中枢神经系统机械和生化损伤后防止神经元死亡的保护作用。这些发现揭示了控制 Treg 的生理机制，并可能为下调 Treg 活性（例如神经元变性）或增强 Treg 活性（自身免疫性疾病）的新治疗策略开辟道路。
Fighting off neuronal degeneration requires a well controlled T-cell response against self-antigens residing in sites of the CNS damage. The ability to evoke this response is normally suppressed by naturally occurring CD4(+) CD25(+) regulatory T-cells (Treg). No physiological compound that controls Treg activity has yet been identified. Here, we show that dopamine, acting via type 1 dopamine receptors ( found here to be preferentially expressed by Treg), reduces the suppressive activity and the adhesive and migratory abilities of Treg. Treg activity was correlated with activation of the ERK1/2 (extracellular signal-regulated kinase 1/2) signaling pathway. Systemic injection of dopamine or an agonist of its type 1 receptors significantly enhanced, via a T-cell-dependent mechanism, protection against neuronal death after CNS mechanical and biochemical injury. These findings shed light on the physiological mechanisms controlling Treg and might open the way to novel therapeutic strategies for downregulating Treg activity (e.g., in neuronal degeneration) or for strengthening it (in autoimmune diseases).