Inhibitory role for GABA in autoimmune inflammation
Inhibitory role for GABA in autoimmune inflammation
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DOI：
10.1073/pnas.0915139107
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发表时间：
2010-02-09
影响因子：
11.1
通讯作者：
Steinman, Lawrence
中科院分区：
文献类型：
--
作者：
Bhat, Roopa;Axtell, Robert;Steinman, Lawrence
GABA是成人大脑中的主要抑制性神经递质，在免疫系统中具有平行的抑制作用。我们证明了免疫细胞合成GABA并具有GABA催化剂的机制。抗原递呈细胞（APC）表达功能性GABA受体并对GABA产生电生理反应。因此，免疫系统含有GABA信号传导的所有必要成分，并且GABA本身可以作为旁分泌或自分泌因子发挥作用。这些观察结果使我们进一步询问GABA通路的操纵是否会影响多发性硬化症的动物模型，实验性自身免疫性脑脊髓炎（EAE）。增加GABA能活性通过抑制炎症改善EAE中的持续性瘫痪。GABA能药物直接作用于APC，减少MAPK信号并减弱随后对髓鞘蛋白的适应性炎症反应。
GABA, the principal inhibitory neurotransmitter in the adult brain, has a parallel inhibitory role in the immune system. We demonstrate that immune cells synthesize GABA and have the machinery for GABA catabolism. Antigen-presenting cells (APCs) express functional GABA receptors and respond electrophysiologically to GABA. Thus, the immune system harbors all of the necessary constituents for GABA signaling, and GABA itself may function as a paracrine or autocrine factor. These observations led us to ask further whether manipulation of the GABA pathway influences an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Increasing GABAergic activity ameliorates ongoing paralysis in EAE via inhibition of inflammation. GABAergic agents act directly on APCs, decreasing MAPK signals and diminishing subsequent adaptive inflammatory responses to myelin proteins.