Augmenting DAF levels in vivo ameliorates experimental autoimmune encephalomyelitis.
Augmenting DAF levels in vivo ameliorates experimental autoimmune encephalomyelitis.
复制标题
提高体内 DAF 水平可改善实验性自身免疫性脑脊髓炎。
DOI：
10.1016/j.molimm.2009.07.003
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发表时间：
2009-09
影响因子：
3.6
通讯作者：
Lin F
中科院分区：
文献类型：
--
作者：
Li Q;Huang D;Nacion K;Bu H;Lin F
最近对实验性自身免疫性脑脊髓炎（EAE）的研究发现，Daf 1-/-小鼠的CNS损伤比野生型（WT）大得多，这表明上调体内β-内酰胺酶水平可能会改善疾病。为了测试这一点，我们培育了一只Daf 1转基因（Tg）小鼠，其细胞表面DAF水平升高。在旁观者C3 b摄取测定中，Daf 1 Tg小鼠红细胞在其表面上摄取的C3 b少于WT红细胞。当与OT-II CD 4 + T细胞和OVA 323 -339肽一起共培养时，DaflTg小鼠骨髓来源的树突状细胞（BM-DC）产生比WT BM-DC更少的C5 a和C3 a，并且刺激更少的T细胞应答。在MOG 35 -55免疫诱导的EAE模型中，与WT相比，Daf 1 Tg小鼠表现出延迟的疾病发作和降低的临床评分。组织学分析表明，有较少的炎症和脱髓鞘在Daf 1 Tg小鼠的脊髓比WT。根据这些结果，Daf 1 Tg小鼠具有降低的MOG 35 -55特异性Th 1和Th 17应答。这些数据提供了进一步的证据，证明EAE中的EAE抑制自身反应性T细胞应答，并表明增加其表达水平在治疗多发性硬化以及其他T细胞介导的疾病中可能是有效的。
Recent studies in experimental autoimmune encephalomyelitis (EAE) have found that CNS injury in Daf1-/- mice is much greater than in wild types (WTs), suggesting that upregulating DAF levels in vivo might ameliorate disease. To test this, we generated a Daf1 transgenic (Tg) mouse which had elevated DAF levels on its cell surfaces. In bystand C3b uptake assays, Daf1 Tg mouse erythrocytes took up less C3b on their surfaces than WT erythrocytes. When co-cultured with OT-II CD4+ T cells together with OVA323-339 peptide, Daf1 Tg mouse bone marrow derived dendritic cells (BM-DCs) produced less C5a and C3a than WT BM-DCs and stimulated a lesser T cell response. In MOG35-55 immunization induced EAE model, Daf1 Tg mice exhibited delayed disease onset and decreased clinical scores compared to WTs. Histological analyses showed that there were less inflammation and demyelination in spinal cords in Daf1 Tg mice than those in WTs. In accordance with these results, Daf1 Tg mice had decreased MOG35-55 specific Th1 and Th17 responses. These data provide further evidence that DAF suppresses autoreactive T cell responses in EAE, and indicate that augmenting its expression levels could be effective therapeutically in treating multiple sclerosis as well as other T cell mediated diseases.
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DOI：
10.1084/jem.20041967
发表时间：
2005-05-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Heeger PS;Lalli PN;Lin F;Valujskikh A;Liu J;Muqim N;Xu Y;Medof ME
通讯作者：
Medof ME
影响因子：
4.4
作者：
Liu, Jinbo;Lin, Feng;Medof, M. Edward
通讯作者：
Medof, M. Edward
影响因子：
4.4
作者：
Sogabe, H;Nangaku, M;Song, WC
通讯作者：
Song, WC
影响因子：
2.7
作者：
Kisseberth, WC;Brettingen, NT;Sandgren, EP
通讯作者：
Sandgren, EP
影响因子：
20.3
作者：
Lalli, Peter N.;Strainic, Michael G.;Heeger, Peter S.
通讯作者：
Heeger, Peter S.