Beta interferon restricts the inflammatory potential of CD4+ cells through the boost of the Th2 phenotype, the inhibition of Th17 response and the prevalence of naturally occurring T regulatory cells
Beta interferon restricts the inflammatory potential of CD4+ cells through the boost of the Th2 phenotype, the inhibition of Th17 response and the prevalence of naturally occurring T regulatory cells
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DOI：
10.1016/j.molimm.2008.06.006
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发表时间：
2008-09-01
影响因子：
3.6
通讯作者：
Ballester, Sara
中科院分区：
文献类型：
--
作者：
Martin-Saavedra, Francisco M.;Gonzalez-Garcia, Coral;Ballester, Sara
β-干扰素（IFN-β）是治疗多发性硬化症（MS）的一种有价值的疗法，其在实验性自身免疫性脑脊髓炎（EAE）的动物模型中也是有效的。然而，解释其在疾病中抗炎活性的准确机制尚未完全揭示。现有数据支持T淋巴细胞是IFN-β的主要细胞靶点之一。我们已经发现，在IFN-β处理下，未定型小鼠幼稚T细胞的体外抗CD 3刺激导致T细胞分化过程向T2表型倾斜，防止与Bcl-x（L）表达增加相关的天然存在的CD 4（+）T调节细胞（nTreg）的凋亡，并降低IL-17表达。从初始CD 4（+）细胞的原代培养物中去除nTreg消除了IFN-β驱动的IL-17的下调，这表明Th 17和nTreg亚群之间的相互作用。在SJL小鼠中诱导的EAE的实验显示了IFN-β处理后脾CD 4（+）CD 25（+）GITR（+）Foxp 3（+）细胞积累的体内证据。另一方面，经治疗的动物显示外周CD 4（+）细胞（Th 17）和MBP特异性脊髓细胞的IL-17表达显著降低。体内和体外结果都指出了IFN-β可以发挥其治疗作用的新靶点。(C)2008爱思唯尔有限公司保留所有权利。
Beta-interferon (IFN-beta) is a valuable therapy for multiple sclerosis (MS) which is also effective in the animal model of experimental autoimmune encephalomyelitis (EAE). However, the accurate mechanisms to explain its anti-inflammatory activity in the disease are not fully revealed. Available data support that T lymphocytes are among the main cell targets of IFN-beta. We have found that in vitro anti-CD3 stimulation of uncommitted murine naive T cells under IFN-beta treatment results in skewing the T cell differentiation process towards the T2 phenotype, in a prevention from apoptosis of naturally occurring CD4(+) T regulatory cells (nTreg) in correlation with an increase in Bcl-x(L) expression, and in a decrease of IL-17 expression. Elimination of nTreg from the primary culture of naive CD4(+) cells abolished the down-regulation of IL-17 driven by IFN-beta, what suggests the interaction between Th17 and nTreg subsets. Experiments in EAE induced in SJL mice, showed in vivo evidence for the accumulation of spleen CD4(+)CD25(+)GITR(+)Foxp3(+) cells after IFN-beta treatment. On the other hand, treated animals showed a striking decrease of IL-17 expression by peripheral CD4(+) cells (Th17) and MBP-specific spinal cord cells. Both the in vivo and in vitro results point out new targets through which IFN-beta could exert its therapeutic action. (C) 2008 Elsevier Ltd. All rights reserved.