Immunomodulation of EAE by alpha-fetoprotein involves elevation of immune cell apoptosis markers and the transcription factor FoxP3
Immunomodulation of EAE by alpha-fetoprotein involves elevation of immune cell apoptosis markers and the transcription factor FoxP3
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DOI：
10.1016/j.jns.2008.12.014
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发表时间：
2009-04-15
影响因子：
4.4
通讯作者：
Brenner, Talma
中科院分区：
文献类型：
--
作者：
Irony-Tur-Sinai, Michal;Grigoriadis, Nikolaos;Brenner, Talma
甲胎蛋白（AFP）是一种与哺乳动物胎儿正常生长相关的免疫调节糖蛋白。 Ws 表明，重组人 AFP (rhAFP) 治疗可降低实验性自身免疫性脑脊髓炎 (EAE) 小鼠的淋巴细胞反应性和神经炎症程度。在本研究中，我们发现 AFP 参与免疫细胞凋亡，证明了其可能的作用机制。 AFP 增加外周淋巴细胞中 Bax、Bid、Bad 和 ApaF 基因的表达，同时增强浸润免疫细胞中 Caspase-3、Fas、FasL 和 TRAIL 的表达。凋亡标记物的诱导伴随着淋巴结细胞中 Foxp3 表达的增加，以及 CNS 中 CD4+Foxp3+ 调节性 T 细胞的积累。总体而言，这些免疫学改变导致疾病较轻并加速了缓解率。我们的结果表明 AFP 在控制与 EAE 相关的自身免疫炎症方面发挥着新作用。 (C) 2008 Elsevier B.V. 保留所有权利。
Alpha-fetoprotein (AFP) is an immunomodulatory glycoprotein associated with the normal growth of the mammalian fetus. Ws have shown that treatment with recombinant human AFP (rhAFP) reduced lymphocyte reactivity and the extent of neuroinflammation in mice with experimental autoimmune encephalomyelitis (EAE). In the present study we found involvement of AFP in immune cell apoptosis, attesting to its possible mechanism of action. AFP increased the expression of the Bax, Bid, Bad and ApaF genes in peripheral lymphocytes, together with an enhanced expression of Caspase-3, Fas, FasL and TRAIL among infiltrating immune cells. The induction of apoptosis markers was accompanied with an increased expression of Foxp3 in lymph node cells, as well as accumulation of CD4+Foxp3+ regulatory T cells in the CNS. Overall, these immunological alterations gave rise to a milder disease and accelerated remission rate. Our results suggest a new role for AFP in controlling the autoimmune inflammation associated with EAE. (C) 2008 Elsevier B.V. All rights reserved.