CardioRespiratory Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
J Leukoc Biol. 2019 Oct;106(4):889-901. doi: 10.1002/JLB.3MR1217-497R. Epub 2019 May 7.
Eosinophilic asthma has conventionally been proposed to be a T helper 2 driven disease but emerging evidence supports a central role of type 2 innate lymphoid cells (ILC2s). These are non-T, non-B cells that lack antigen specificity and produce more IL-5 and IL-13 than CD4 T lymphocytes, on a cell per cell basis, in vitro. Although it is clear that ILC2s and CD4 T cells work in concert with each other to drive type 2 immune responses, kinetic studies in allergic asthma suggest that ILC2s may act locally within the airways to "initiate" eosinophilic responses, whereas CD4 T cells act locally and systemically to "perpetuate" eosinophilic inflammatory responses. Importantly, ILC2s are increased within the airways of severe asthmatics, with the greatest number of IL-5 IL-13 ILC2s being detected in sputum from severe asthmatics with uncontrolled eosinophilia despite high-dose steroid therapy. Although the precise relationship between ILC2s and steroid sensitivity in asthma remains unclear, controlling the activation of ILC2s within the airways may provide an effective therapeutic target for eosinophilic inflammation in airways diseases.
嗜酸性粒细胞性哮喘传统上被认为是 T 辅助 2 驱动的疾病，但新出现的证据支持 2 型先天淋巴样细胞（ILC2）的核心作用。这些是非 T、非 B 细胞，缺乏抗原特异性，并且在体外，基于细胞的基础上比 CD4 T 淋巴细胞产生更多的 IL-5 和 IL-13。虽然很明显 ILC2 和 CD4 T 细胞协同作用以驱动 2 型免疫反应，但过敏性哮喘的动力学研究表明，ILC2 可能在气道内局部作用以“启动”嗜酸性粒细胞反应，而 CD4 T 细胞在气道内和全身作用以“维持”嗜酸性炎症反应。重要的是，在严重哮喘患者的气道中，ILC2 增加，在尽管接受高剂量类固醇治疗但嗜酸性粒细胞增多仍未得到控制的严重哮喘患者的痰中，检测到最多的 IL-5+IL-13+ILC2。虽然 ILC2 和哮喘中类固醇敏感性之间的确切关系尚不清楚，但控制气道内 ILC2 的激活可能为气道疾病中的嗜酸性粒细胞炎症提供有效的治疗靶点。
