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一种显示出增强胸腺生成能力的白细胞介素-7融合蛋白。

An IL-7 fusion protein that shows increased thymopoietic ability.

作者信息

Henson Sian M, Snelgrove Robert, Hussell Tracy, Wells Dominic J, Aspinall Richard

机构信息

Department of Immunology, Imperial College, Chelsea and Westminster Hospital, London, United Kingdom.

出版信息

J Immunol. 2005 Sep 15;175(6):4112-8. doi: 10.4049/jimmunol.175.6.4112.

Abstract

The role of IL-7 during thymopoiesis has led to it being the focus of a number of therapeutic interventions. However, its small size and pleiotropic nature present problems for thymus-directed therapies. We have created a fusion molecule between the extracellular N-terminal domain of CCR9 and IL-7, which has the potential to overcome these difficulties. This novel fusion protein retains the thymopoietic activity of IL-7 and the ligand-binding ability of CCR9. As a thymopoietic agent, compared with IL-7, it shows an enhanced retention in the thymus, increased de novo T cell production, and increased thymic output. Old mice receiving the fusion protein show improved CD8 T cell responses and reduced viral load after infection with influenza virus compared with those receiving IL-7. This chimeric molecule offers a novel therapeutic strategy that may result in the production of an effective immunorestorative agent.

摘要

白细胞介素-7(IL-7)在胸腺生成过程中的作用使其成为多种治疗干预措施的焦点。然而,其体积小和多效性的特点给针对胸腺的治疗带来了问题。我们构建了趋化因子受体9(CCR9)细胞外N端结构域与IL-7之间的融合分子,它有可能克服这些困难。这种新型融合蛋白保留了IL-7的胸腺生成活性和CCR9的配体结合能力。作为一种胸腺生成剂,与IL-7相比,它在胸腺中的保留时间延长,新生T细胞产生增加,胸腺输出增加。与接受IL-7的老年小鼠相比,接受融合蛋白的老年小鼠在感染流感病毒后表现出改善的CD8 T细胞反应和降低的病毒载量。这种嵌合分子提供了一种新的治疗策略,可能会产生一种有效的免疫恢复剂。

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