Regulatory T Cells and Their Derived Cytokine, Interleukin-35, Reduce Pain in Experimental Autoimmune Encephalomyelitis
Regulatory T Cells and Their Derived Cytokine, Interleukin-35, Reduce Pain in Experimental Autoimmune Encephalomyelitis
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DOI：
10.1523/jneurosci.1815-18.2019
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发表时间：
2019-03-20
影响因子：
5.3
通讯作者：
Moalem-Taylor, Gila
中科院分区：
文献类型：
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作者：
Duffy, Samuel S.;Keating, Brooke A.;Moalem-Taylor, Gila
感觉问题，如神经性疼痛是多发性硬化症（MS）的常见和衰弱的症状，一种中枢神经系统的自身免疫性炎症性疾病。调节性T（Treg）细胞对于维持免疫稳态至关重要，但它们在MS相关疼痛中的作用仍然未知。在这里，我们证明了Treg细胞消融足以引发免疫雌性小鼠的实验性自身免疫性脑脊髓炎（EAE）和面部异常性疼痛。在EAE诱导的雌性小鼠中，Treg细胞的过继转移和Treg细胞因子白细胞介素-35（IL-35）的脊髓递送显著降低了面部刺激诱发的疼痛和自发性疼痛，与疾病严重程度无关，并增加了面部伤害性通路的髓鞘形成。鞘内IL-35治疗的效果是Treg细胞依赖性的，并与CNS浸润淋巴细胞中IL-10表达上调和三叉神经传入通路中单核细胞浸润减少相关。我们提出的证据表明，Treg细胞和IL-35通过减少神经炎症和增加髓鞘形成，在减轻与EAE相关的疼痛方面具有有益的作用，与运动症状无关。
Sensory problems such as neuropathic pain are common and debilitating symptoms in multiple sclerosis (MS), an autoimmune inflammatory disorder of the CNS. Regulatory T (Treg) cells are critical for maintaining immune homeostasis, but their role in MS-associated pain remains unknown. Here, we demonstrate that Treg cell ablation is sufficient to trigger experimental autoimmune encephalomyelitis (EAE) and facial allodynia in immunized female mice. In EAE-induced female mice, adoptive transfer of Treg cells and spinal delivery of the Treg cell cytokine interleukin-35 (IL-35) significantly reduced facial stimulus-evoked pain and spontaneous pain independent of disease severity and increased myelination of the facial nociceptive pathway. The effects of intrathecal IL-35 therapy were Treg-cell dependent and associated with upregulated IL-10 expression in CNS-infiltrating lymphocytes and reduced monocyte infiltration in the trigeminal afferent pathway. We present evidence for a beneficial role of Treg cells and IL-35 in attenuating pain associated with EAE independently of motor symptoms by decreasing neuroinflammation and increasing myelination.