Allergic airway diseases are caused by inappropriate immune responses directed against inhaled environmental antigens. We previously reported that the inhibition of diacylglycerol (DAG) kinase ζ (DGKζ), an enzyme that terminates DAG-mediated signaling, protects against T cell-mediated allergic airway inflammation by blocking Th2 cell differentiation. In this study, we tested whether DGKζ deficiency also affects allergic airway disease mediated by type 2 innate lymphoid cells (ILC2)s. DGKζ-deficient mice displayed diminished ILC2 function and reduced papain-induced airway inflammation compared to wildtype mice. Unexpectedly, however, mice with hematopoietic cell-specific deletion of DGKζ displayed intact airway inflammation upon papain challenge. Rather, bone marrow chimera studies revealed that DGKζ deficiency in the non-hematopoietic compartment was responsible for the reduction in papain-induced airway inflammation. These data suggest that DGK might represent a novel therapeutic target not only for T cell-dependent but also ILC2-dependent allergic airway inflammation by affecting non-hematopoietic cells.

过敏性气道疾病是由针对吸入环境抗原的不当免疫反应引起的。我们之前报道过，抑制二酰甘油 (DAG) 激酶 z (DGK z)（ 一种终止 DAG 介导的信号传导的酶）可 通过阻止 Th2 细胞分化来预防 T 细胞介导的过敏性气道炎症。 在这项研究中，我们测试了 DGKζ 缺乏是否也会影响由 2 型先天淋巴细胞 (ILC2) 介导的过敏性气道疾病。与野生型小鼠相比，DGKδ 缺陷小鼠表现出 ILC2 功能减弱和木瓜蛋白酶诱导的气道炎症减少。然而，出乎意料的是，造血细胞特异性缺失 DGK z 的小鼠在木瓜蛋白酶攻击后表现出完整的气道炎症。相反，骨髓嵌合体研究表明， 非造血室中的 DGKζ 缺乏是木瓜蛋白酶诱导的气道炎症减少的原因。这些数据表明，DGK 可能代表一种新的治疗靶点，不仅可以通过影响非造血细胞来治疗 T 细胞依赖性的过敏性气道炎症，还可以治疗 ILC2 依赖性的过敏性气道炎症。