Regulatory T cells attenuate neuropathic pain following peripheral nerve injury and experimental autoimmune neuritis
Regulatory T cells attenuate neuropathic pain following peripheral nerve injury and experimental autoimmune neuritis
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DOI：
10.1016/j.pain.2012.06.005
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发表时间：
2012-09-01
期刊：
影响因子：
7.4
通讯作者：
Moalem-Taylor, Gila
中科院分区：
文献类型：
--
作者：
Austin, Paul J.;Kim, Cristina F.;Moalem-Taylor, Gila
神经病理性疼痛中的神经免疫串扰是神经系统损伤后疼痛过敏的关键因素。CD4+CD25+Foxp3+调节性T细胞(Tregs)是内源性免疫抑制因子，减少T细胞增殖和促炎细胞因子的产生。目前，Tregs在神经病理性疼痛中的作用尚不清楚。本研究在大鼠坐骨神经慢性压迫性损伤和实验性自身免疫性神经炎两种神经病模型上，观察了扩张Tregs对疼痛超敏反应和神经炎症的影响。慢性缩窄性损伤后，用Treg群体扩张剂CD28超激动剂(CD28SupA)治疗后，大鼠淋巴组织、损伤的坐骨神经和腰髓中的Tregs显著增加。CD28SupA治疗后，坐骨神经和背根神经节中浸润性T细胞、巨噬细胞和抗原提呈细胞的数量明显减少，机械性疼痛过敏反应明显降低。在实验性自身免疫性神经炎影响的大鼠中，CD28SupA治疗显著改善了疾病严重程度和机械性疼痛过敏。这与坐骨神经和背根神经节中T细胞、巨噬细胞和抗原提呈细胞的数量减少以及小胶质细胞的激活和T细胞在脊髓中的渗透减少有关。此外，在部分结扎坐骨神经的小鼠中，CD25抗体耗尽Tregs会导致长时间的机械性疼痛超敏反应。这些发现表明，Tregs在神经病理性疼痛的内源性恢复中起作用。因此，这个T细胞亚群可能是专门针对缓解慢性神经病理性疼痛的。(C)2012年国际疼痛研究协会。爱思唯尔出版，版权所有。
Neuroimmune crosstalk in neuropathic pain is a key contributor to pain hypersensitivity following nervous system injury. CD4+CD25+Foxp3+ regulatory T cells (Tregs) are endogenous immune suppressors, reducing T-cell proliferation and proinflammatory cytokine production. Currently, the role of Tregs in neuropathic pain is unknown. In this study, we tested the effects of expanding Tregs on pain hypersensitivity and neuroinflammation in 2 models of neuropathy; sciatic nerve chronic constriction injury and experimental autoimmune neuritis in rats. Following chronic constriction injury, treatment with CD28 superagonist (CD28SupA), a Treg population expander, significantly increased Tregs in the lymphoid tissues, injured sciatic nerve, and lumbar spinal cord of rats. CD28SupA treatment led to a significant reduction in mechanical pain hypersensitivity, alongside a decrease in the numbers of infiltrating T cells, macrophages, and antigen-presenting cells in the sciatic nerve and dorsal root ganglia. In experimental autoimmune neuritis-affected rats, CD28SupA treatment resulted in a significant improvement in disease severity and in mechanical pain hypersensitivity. This was associated with a reduction in the numbers of T cells, macrophages, and antigen-presenting cells in the sciatic nerve and dorsal root ganglia, and reduced activation of microglia and infiltration of T cells in the spinal cord. Furthermore, depletion of Tregs by a CD25 antibody in mice with a partial sciatic nerve ligation resulted in prolonged mechanical pain hypersensitivity. These findings suggest that Tregs play a role in endogenous recovery from neuropathy-induced pain. Thus, this T-cell subset may be specifically targeted to alleviate chronic neuropathic pain. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.