Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Adv Immunol. 2018;138:1-34. doi: 10.1016/bs.ai.2018.03.001. Epub 2018 Apr 22.
Human eosinophils have characteristic morphologic features, including a bilobed nucleus and cytoplasmic granules filled with cytotoxic and immunoregulatory proteins that are packaged in a specific manner. Eosinophil production in the bone marrow is exquisitely regulated by timely expression of a repertoire of transcription factors that work together via collaborative and hierarchical interactions to direct eosinophil development. In addition, proper granule formation, which occurs in a spatially organized manner, is an intrinsic checkpoint that must be passed for proper eosinophil production to occur. In eosinophil-associated disorders, eosinophils and their progenitors can be recruited in large numbers into tissues where they can induce proinflammatory organ damage in response to local signals. Eosinophils are terminally differentiated and do not proliferate once they leave the bone marrow. The cytokine IL-5 specifically enhances eosinophil production and, along with other mediators, promotes eosinophil activation. Indeed, eosinophil depletion with anti-IL-5 or anti-IL-5Rα is now proven to be clinically beneficial for several eosinophilic disorders, most notably severe asthma, and several therapeutics targeting eosinophil viability and production are now in development. Significant progress has been made in our understanding of eosinophil development and the consequences of tissue eosinophilia. Future research efforts focused on basic eosinophil immunobiology and translational efforts to assist in the diagnosis, treatment selection, and resolution of eosinophil-associated disorders will likely be informative and clinically helpful.
人嗜酸性粒细胞具有特征性的形态学特征，包括双核和细胞质颗粒，其中充满细胞毒性和免疫调节蛋白，这些蛋白以特定的方式包装。骨髓中嗜酸性粒细胞的产生受到严格调控，通过及时表达一系列转录因子来实现，这些转录因子通过协同和层次相互作用共同作用，指导嗜酸性粒细胞的发育。此外，适当的颗粒形成是一个内在的检查点，必须通过该检查点才能正确地产生嗜酸性粒细胞。在与嗜酸性粒细胞相关的疾病中，大量的嗜酸性粒细胞及其前体细胞可以被招募到组织中，在那里它们可以响应局部信号诱导炎症性器官损伤。嗜酸性粒细胞是终末分化的，一旦离开骨髓就不会增殖。细胞因子 IL-5 特异性地增强嗜酸性粒细胞的产生，并与其他介质一起促进嗜酸性粒细胞的激活。事实上，用抗 IL-5 或抗 IL-5Rα 耗竭嗜酸性粒细胞已被证明对几种嗜酸性粒细胞相关疾病（尤其是严重哮喘）具有临床益处，目前有几种针对嗜酸性粒细胞活力和产生的治疗方法正在开发中。我们对嗜酸性粒细胞发育和组织嗜酸性粒细胞增多的后果的理解已经取得了重大进展。未来的研究工作集中在基础嗜酸性粒细胞免疫生物学上，并努力进行转化，以协助诊断、治疗选择和解决与嗜酸性粒细胞相关的疾病，这可能具有启发性和临床帮助。
