Divergent roles for p55 and p75 tumor necrosis factor receptors in the pathogenesis of MOG35-55-induced experimental autoimmune encephalomyelitis
Divergent roles for p55 and p75 tumor necrosis factor receptors in the pathogenesis of MOG35-55-induced experimental autoimmune encephalomyelitis
复制标题
DOI：
10.1006/cimm.2000.1706
复制
发表时间：
2000-10-10
影响因子：
4.3
通讯作者：
Miller, SD
中科院分区：
文献类型：
--
作者：
Suvannavejh, GC;Lee, HO;Miller, SD
为了阐明肿瘤坏死因子（TNF）在自身免疫炎症方面的作用及其在自身反应性效应细胞凋亡消除中的潜在作用，我们评估了p55（TNFR 1/Tnfrsf 1a/CD 120 a）和p75（TNFR 2/Tnfrsf 1b/CD 120 b）TNF受体在MOG（35-55）诱导的实验性自身免疫性脑脊髓炎（EAE）发病机制中的作用。TNFR p55/p75（-/-）双敲除小鼠对临床疾病完全抵抗。TNFR p55（-/-）单敲除小鼠也完全抵抗EAE，表现出降低的MOG（35.55）（..）特异性增殖反应和Th 1细胞因子产生，尽管显示出等同的DTH反应。重要的是，IL-5在p55-/-小鼠中显著增加。相反，p75（-/-）基因敲除小鼠表现出EAE加重，Th 1细胞因子产生增加，CD 4（+）和F4/80（+）CNS浸润增加。因此，p55/TNFR 1是病理性疾病的起始所必需的，而p75/TNFR 2在调节免疫应答中可能是重要的。这些结果对靶向p55和p75受体治疗自身免疫性疾病具有重要意义。(C)北京大学出版社.
To clarify the role of tumor necrosis factor (TNF) in the inflammatory aspects of autoimmunity vs its potential role in the apoptotic elimination of autoreactive effector cells, we assessed the roles of the p55 (TNFR1/Tnfrsf1a/CD120a) and p75 (TNFR2/ Tnfrsf1b/CD120b) TNF receptors in the pathogenesis of MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE). TNFR p55/p75(-/-) double knockout mice were completely resistant to clinical disease. TNFR p55(-/-) single knockout mice were also totally resistant to EAE, exhibiting reduced MOG(35.55)(..) specific proliferative responses and Th1 cytokine production, despite displaying equivalent DTH responses. Importantly, IL-5 was significantly increased in p55-/- mice. In contrast, p75(-/-) knockout mice exhibited exacerbated EAE, enhanced Th1 cytokine production, and enhanced CD4(+) and F4/80(+) CNS infiltration. Thus, p55/TNFR1 is required for the initiation of pathologic disease, whereas p75/ TNFR2 may be important in regulating the immune response. These results have important implications for therapies targeting p55 and p75 receptors for treatingautoimmune diseases. (C) 2000 Academic Press.