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嗜酸性粒细胞敲除人类:通过靶向嗜酸性粒细胞的生物治疗揭示嗜酸性粒细胞的作用。

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies.

机构信息

Division of Allergy, Asthma and Clinical Immunology, Mayo Clinic, Scottsdale, Arizona 85259, USA; email:

Guy's and St Thomas' Hospitals, London WC2R 2LS, United Kingdom; email:

出版信息

Annu Rev Immunol. 2021 Apr 26;39:719-757. doi: 10.1146/annurev-immunol-093019-125918. Epub 2021 Mar 1.

Abstract

The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Researchers using eosinophil knockout mice have identified a contributory role for eosinophils in basal and inflammatory processes and protective immunity. Primarily fueled by the purported proinflammatory role of eosinophils in eosinophil-associated diseases, a series of anti-eosinophil therapeutics have emerged as a new class of drugs. These agents, which dramatically deplete eosinophils, provide a valuable opportunity to characterize the consequences of eosinophil knockout humans. Herein, we comparatively describe mouse and human eosinophil knockouts. We put forth the view that human eosinophils negatively contribute to a variety of diseases and, unlike mouse eosinophils, do not yet have an identified role in physiological health; thus, clarifying all roles of eosinophils remains an ongoing pursuit.

摘要

神秘的嗜酸性粒细胞作为免疫系统的一个令人兴奋的组成部分而出现,参与了大量的体内平衡和炎症反应。通过体内操纵嗜酸性粒细胞的实验系统,在最初的小鼠和最近的人类中取得了实质性的进展。研究人员使用嗜酸性粒细胞敲除小鼠已经确定了嗜酸性粒细胞在基础和炎症过程以及保护性免疫中的贡献作用。主要是由于嗜酸性粒细胞在与嗜酸性粒细胞相关的疾病中的假定促炎作用,一系列抗嗜酸性粒细胞治疗药物已经作为一类新药出现。这些药物可以显著消耗嗜酸性粒细胞,为研究嗜酸性粒细胞敲除的人类的后果提供了一个有价值的机会。在此,我们比较性地描述了小鼠和人类的嗜酸性粒细胞敲除。我们提出这样的观点,即人类嗜酸性粒细胞对多种疾病有负面影响,与小鼠嗜酸性粒细胞不同,它们在生理健康中尚未确定有作用;因此,澄清嗜酸性粒细胞的所有作用仍然是一个持续的追求。

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