TNF-α receptor 1 deficiency reduces antigen-presenting capacity of Schwann cells and ameliorates experimental autoimmune neuritis in mice
TNF-α receptor 1 deficiency reduces antigen-presenting capacity of Schwann cells and ameliorates experimental autoimmune neuritis in mice
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DOI：
10.1016/j.neulet.2009.12.045
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发表时间：
2010-02-05
影响因子：
2.5
通讯作者：
Zhu, Jie
中科院分区：
文献类型：
--
作者：
Mao, Xi-Jing;Zhang, Xing-Mei;Zhu, Jie
肿瘤坏死因子-α (TNF-α) 是一种多效性促炎细胞因子，具有潜在的神经破坏作用，在自身免疫性脱髓鞘疾病中发挥着关键作用。为了阐明 TNF-α 在实验性自身免疫性神经炎 (EAN) 发病机制中的作用，本研究调查了 TNF-α 受体 1 缺陷 (TNFR1(-/-)) 小鼠中 PO 蛋白肽 106-125 诱导的 EAN 中雪旺细胞 (SC) 的抗原呈递能力。通过活化的 SC 上 MHC II 类 (MHCII)、CD40、CD80 和 CD86 分子的表达以及 PO 蛋白肽 106-125 特异性 T 细胞与活化的 SC 共培养物中 T 细胞增殖的诱导来评估 SC 的抗原呈递能力。此外，通过流式细胞术测量激活的 SC 中诱导型一氧化氮合酶 (iNOS) 的表达。与野生型 EAN 小鼠相比，TNFR1(-/-) EAN 小鼠的 EAN 临床症状明显延迟并减少。与此同时，与野生型小鼠相比，TNFR1(-/-)小鼠SCs上MHCII、CD80和iNOS的表达降低。同样，TNFR1(-/-) EAN小鼠的活化SC模拟的PO蛋白肽106-125特异性T细胞的增殖低于野生型EAN小鼠。我们的数据表明，TNF-α 可能通过 TNFR1 上调 SC 的抗原呈递功能和 iNOS 产生，在 EAN 中发挥促炎作用。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic pro-inflammatory cytokine with potentially neurodestructive effects and plays a pivotal role in autoimmune demyelinating disease. To address the role of TNF-alpha in the pathogenesis of experimental autoimmune neuritis (EAN), the current study investigated the antigen-presenting capacity of Schwann cells (SCs) in EAN induced by PO protein peptide 106-125 in TNF-alpha recepter 1 deficient (TNFR1(-/-)) mice. The antigen-presenting capacity of SCs was assessed by the expression of MHC class II (MHCII), CD40, CD80 and CD86 molecules on activated SCs as well as by induction of T cell proliferation in co-cultures of PO protein peptide 106-125 specific T cells with activated SCs. In addition, the expression of inducible nitric oxide synthase (iNOS) was measured in activated SCs by flow cytometry. TNFR1(-/-) EAN mice developed significantly delayed and reduced clinical signs of EAN compared to wild type EAN mice. In parallel, the expression of MHCII, CD80 and iNOS on SCs were decreased in TNFR1(-/-) mice compared to wild type mice. Likewise, proliferation of PO protein peptide 106-125 specific T cells simulated by activated SCs of TNFR1(-/-) EAN mice was lower than that of wild type EAN mice. Our data suggest that TNF-alpha may exert pro-inflammatory effects in EAN via TNFR1 by up-regulating the antigen-presenting function and iNOS production of SCs. (C) 2009 Elsevier Ireland Ltd. All rights reserved.