The tick saliva immunosuppressor, Salp15, contributes to Th17-induced pathology during Experimental Autoimmune Encephalomyelitis.
The tick saliva immunosuppressor, Salp15, contributes to Th17-induced pathology during Experimental Autoimmune Encephalomyelitis.
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DOI：
10.1016/j.bbrc.2010.09.125
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发表时间：
2010-11-05
影响因子：
3.1
通讯作者：
Anguita J
中科院分区：
文献类型：
--
作者：
Juncadella IJ;Bates TC;Suleiman R;Monteagudo-Mera A;Olson CM Jr;Navasa N;Olivera ER;Osborne BA;Anguita J
Salp15是壁虱唾液中的一种蛋白，它通过与CD4相互作用来抑制CD4+T细胞的分化。该蛋白抑制T细胞激活和IL-2产生过程中的早期信号事件。由于小鼠实验性自身免疫性脑脊髓炎的发生是由中枢神经系统渗入的针对髓鞘相关蛋白的CD4+T细胞介导的，我们试图确定在EAE诱导期间用Salp15治疗小鼠是否可以防止促炎T细胞反应的产生和疾病的发展。令人惊讶的是，Salp15处理的小鼠比对照小鼠患上了更严重的EAE。用扁虱唾液蛋白处理EAE诱导的小鼠，没有导致T细胞向中枢神经系统的渗透增加，表明Salp15没有影响血脑屏障的通透性。Salp15处理不影响针对诱导肽的抗体反应的产生，也不影响血清中干扰素γ的存在。然而，Salp15治疗导致Th17细胞在体内的分化增加，从中枢神经系统和外周分离的PLP139-151特异性CD4+T细胞产生更高的IL-17证明了这一点。在体外，Salp15能在有IL-6和无转化生长因子β的情况下诱导Th17细胞分化。这些结果表明，在T细胞分化过程中，通过抑制IL-2的产生，可以获得一个传导的分化环境，这一作用可能是通过转化生长因子β和其他免疫抑制剂来实现的。
Salp15 is a tick saliva protein that inhibits CD4+ T cell differentiation through its interaction with CD4. The protein inhibits early signaling events during T cell activation and IL-2 production. Because murine experimental autoimmune encephalomyelitis development is mediated by central nervous system-infiltrating CD4+ T cells that are specific for myelin-associated proteins, we sought to determine whether the treatment of mice with Salp15 during EAE induction would prevent the generation of proinflammatory T cell responses and the development of the disease. Surprisingly, Salp15-treated mice developed more severe EAE than control animals. The treatment of EAE-induced mice with the tick saliva protein did not result in increased infiltration of T cells to the central nervous system, indicating that Salp15 had not affected the permeability of the blood-brain barrier. Salp15 treatment did not affect the development of antibody responses against the eliciting peptide or the presence of IFNγ in the sera. The treatment with Salp15 resulted, however, in the increased differentiation of Th17 cells in vivo, as evidenced by higher IL-17 production from PLP139-151-specific CD4+ T cells isolated from the central nervous system and the periphery. In vitro, Salp15 was able to induce the differentiation of Th17 cells in the presence of IL-6 and the absence of TGFβ These results suggest that a conductive milieu for the differentiation of Th17 cells can be achieved by restriction of the production of IL-2 during T cell differentiation, a role that may be performed by TGFβ and other immunosuppressive agents.
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影响因子：
64.5
作者：
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通讯作者：
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作者：
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