Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901.
Rutgers Graduate School of Biomedical Sciences, Piscataway, NJ 08854.
J Immunol. 2019 Sep 1;203(5):1230-1241. doi: 10.4049/jimmunol.1900068. Epub 2019 Jul 31.
Basophils are innate immune cells associated with type 2 immunity, allergic reactions, and host defense against parasite infections. In this study, we show that the transcription factor PLZF, which is known for its essential role in the function and development of several innate lymphocyte subsets, is also important for the myeloid-derived basophil lineage. PLZF-deficient mice had decreased numbers of basophil progenitors in the bone marrow and mature basophils in multiple peripheral tissues. Functionally, PLZF-deficient basophils were less responsive to IgE activation and produced reduced amounts of IL-4. The altered function of basophils resulted in a blunted Th2 T cell response to a protein allergen. Additionally, PLZF-deficient basophils had reduced expression of the IL-18 receptor, which impacted migration to lungs. PLZF, therefore, is a major player in controlling type 2 immune responses mediated not only by innate lymphocytes but also by myeloid-derived cells.
嗜碱性粒细胞是与 2 型免疫、过敏反应和宿主防御寄生虫感染相关的固有免疫细胞。在这项研究中,我们表明,转录因子 PLZF 已知在几个固有淋巴细胞亚群的功能和发育中发挥重要作用,对于髓系来源的嗜碱性粒细胞谱系也很重要。PLZF 缺陷小鼠的骨髓中嗜碱性粒细胞前体和多个外周组织中的成熟嗜碱性粒细胞数量减少。功能上,PLZF 缺陷的嗜碱性粒细胞对 IgE 激活的反应性降低,产生的 IL-4 减少。嗜碱性粒细胞功能的改变导致对蛋白质过敏原的 Th2 T 细胞反应减弱。此外,PLZF 缺陷的嗜碱性粒细胞表达的 IL-18 受体减少,这影响了向肺部的迁移。因此,PLZF 是控制 2 型免疫反应的主要参与者,不仅由固有淋巴细胞介导,也由髓系来源的细胞介导。