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首页> 外文期刊>Annual Review of Immunology >Insights into Cytokine-Receptor Interactions from Cytokine Engineering
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Insights into Cytokine-Receptor Interactions from Cytokine Engineering

机译：来自细胞因子工程的细胞因子受体相互作用的见解

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摘要

Cytokines exert a vast array of immunoregulatory actions critical to human biology and disease. However, the desired immunotherapeutic effects of native cytokines are often mitigated by toxicity or lack of efficacy, either of which results from cytokine receptor pleiotropy and/or undesired activation of off-target cells. As our understanding of the structural principles of cytokine receptor interactions has advanced, mechanism-based manipulation of cytokine signaling through protein engineering has become an increasingly feasible and powerful approach. Modified cytokines, both agonists and antagonists, have been engineered with narrowed target cell specificities, and they have also yielded important mechanistic insights into cytokine biology and signaling. Here we review the theory and practice of cytokiine engineering and rationalize the mechanisms of several engineered cytokines in the context of structure. We discuss specific examples of how structure-based cytokine engineering has opened new opportunities for cytokines as drugs, with a focus on the immunotherapeutic cytokines interferon, interleukin-2, and interleukin -4.
机译：细胞因子对人类生物学和疾病发挥了广泛的免疫调节作用。然而，通常通过毒性或缺乏疗效来减轻天然细胞因子的所需的免疫治疗效果，其中来自细胞因子受体肺活动和/或不期望的脱靶细胞的激活结果。由于我们对细胞因子受体相互作用的结构原理进行了先进的，基于机制的细胞因子信号传导通过蛋白质工程的操纵已成为日益可行和强大的方法。修饰的细胞因子，两个激动剂和拮抗剂都被设计成狭窄的靶细胞特异性，并且它们也对细胞因子生物学和信号传导产生了重要的机制见解。在这里，我们回顾了Cytokiine Engineering的理论和实践，并在结构背景下的若干工程细胞因子的机制合理化。我们讨论了基于结构的细胞因子工程如何为药物开辟新机会的具体例子，以免疫治疗细胞因子干扰素，白细胞介素-2和白细胞介素-4。

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