Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
EMBO Mol Med. 2018 Apr;10(4). doi: 10.15252/emmm.201708657.
House dust mite (HDM)-allergic asthma is driven by T helper 2 (Th2) lymphocytes, but also innate immune cells control key aspects of the disease. The precise function of innate natural killer (NK) cells during the initiation and propagation of asthma has been very confusing, in part because different, not entirely specific, strategies were used to target these cells. We show that HDM inhalation rapidly led to the accumulation of NK cells in the lung-draining lymph nodes and of activated CD69 NK cells in the bronchoalveolar lumen. However, genetically engineered -DTA or -DTR mice that constitutively or temporarily lack NK cells, still developed all key features of acute or chronic HDM-driven asthma, such as bronchial hyperreactivity, Th2 cytokine production, eosinophilia, mucus overproduction, and Th2-dependent immunoglobulin serum titers. The same results were obtained by administration of conventional NK1.1 or asialo-GM1 NK cell-depleting antibodies, antibody-mediated blocking of the NKG2D receptor, or genetic NKG2D deficiency. Thus, although NK cells accumulate in allergen-challenged lungs, our findings comprehensively demonstrate that these cells are not required for HDM-driven asthma in the mouse.
屋尘螨（HDM）-过敏哮喘是由辅助性 T 细胞 2（Th2）淋巴细胞驱动的，但固有免疫细胞也控制着疾病的关键方面。固有自然杀伤（NK）细胞在哮喘的起始和发展中的精确功能一直非常令人困惑，部分原因是使用了不同的、不完全特异的策略来靶向这些细胞。我们表明，HDM 吸入可迅速导致引流淋巴结中 NK 细胞的积累和支气管肺泡腔中活化的 CD69 NK 细胞的积累。然而，经过基因工程改造的 -DTA 或 -DTR 小鼠，无论是组成型还是暂时性缺乏 NK 细胞，仍然发展出所有急性或慢性 HDM 驱动的哮喘的关键特征，如支气管高反应性、Th2 细胞因子产生、嗜酸性粒细胞增多、黏液过度产生和 Th2 依赖性免疫球蛋白血清滴度。通过给予常规的 NK1.1 或无唾液酸 GM1 NK 细胞耗竭抗体、NKG2D 受体的抗体介导阻断或遗传 NKG2D 缺陷也得到了相同的结果。因此，尽管 NK 细胞在过敏原挑战的肺部中积累，但我们的研究结果全面表明，这些细胞不是小鼠 HDM 驱动的哮喘所必需的。
