Uncoupling the proinflammatory from the immunosuppressive properties of tumor necrosis factor (TNF) at the p55 TNF receptor level: implications for pathogenesis and therapy of autoimmune demyelination.
Uncoupling the proinflammatory from the immunosuppressive properties of tumor necrosis factor (TNF) at the p55 TNF receptor level: implications for pathogenesis and therapy of autoimmune demyelination.
复制标题
DOI：
10.1084/jem.193.4.427
复制
发表时间：
2001-02-19
期刊：
影响因子：
--
通讯作者：
Kollias G
中科院分区：
文献类型：
--
作者：
Kassiotis G;Kollias G
多发性硬化症（MS）是一种中枢神经系统的致残性炎性脱髓鞘疾病，被认为是由于对髓鞘抗原的自身反应性。肿瘤坏死因子（TNF）和p55 TNF受体（TNFR）在MS发病机制中有很强的牵连。在这项研究中，我们揭示了TNF在实验性自身免疫性脑脊髓炎（EAE）中的双重作用，EAE是MS的小鼠模型。除了其良好的促炎作用外，TNF还表现出有效的免疫抑制特性，为MS的抗TNF治疗的免疫和疾病激活作用提供了一种可能的解释。髓鞘特异性T细胞反应性不能消退，并且活化/记忆T细胞的扩增异常延长，导致加重的EAE。引人注目的是，TNF的免疫抑制和对EAE的保护不需要p55 TNFR，而在疾病的急性期，TNF的有害作用需要相同的受体。因此，阻断p55 TNFR在自身免疫性脱髓鞘中的功能可以抑制TNF的有害促炎活性而不损害其免疫抑制特性。
Multiple sclerosis (MS) is a disabling inflammatory demyelinating disease of the central nervous system, considered to result from self-reactivity to myelin antigens. Tumor necrosis factor (TNF) and the p55 TNF receptor (TNFR) have been strongly implicated in MS pathogenesis. We reveal in this study a dual role for TNF in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. In addition to its well-established proinflammatory effects, TNF exhibits potent immunosuppressive properties, providing one possible explanation for the immune and disease activating effect of anti-TNF treatment of MS. We show that in TNF-deficient mice, myelin-specific T cell reactivity fails to regress and expansion of activated/memory T cells is abnormally prolonged, leading to exacerbated EAE. Strikingly, immnosuppression by TNF and protection against EAE does not require the p55 TNFR, whereas the same receptor is necessary for the detrimental effects of TNF during the acute phase of the disease. Thus, blocking the function of the p55 TNFR in autoimmune demyelination may inhibit the noxious proinflammatory activities of TNF without compromising its immunosuppressive properties.
登录
查看更多内容
影响因子：
32.4
作者：
McSorley, SJ;Soldera, S;Glaichenhaus, N
通讯作者：
Glaichenhaus, N
影响因子：
15.3
作者：
Tuohy, VK;Yu, M;Kinkel, RP
通讯作者：
Kinkel, RP
影响因子：
64.8
作者：
JACOB, CO;MCDEVITT, HO
通讯作者：
MCDEVITT, HO
影响因子：
5.4
作者：
Speiser, DE;Sebzda, E;Ohashi, PS
通讯作者：
Ohashi, PS
影响因子：
64.8
作者：
ROTHE, J;LESSLAUER, W;BLUETHMANN, H
通讯作者：
BLUETHMANN, H