Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Division of Critical Care Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Allergol Int. 2019 Apr;68(2):143-149. doi: 10.1016/j.alit.2018.11.006. Epub 2018 Dec 17.
Asthma is a highly prevalent heterogeneous inflammatory disorder of the airways. Not all patients respond to anti-inflammatory treatment with corticosteroids, leading to significant morbidity in severe asthma. Much attention has been paid to defining the cellular and molecular mechanisms of type 2 inflammation that are operative in asthma. Development of targeted therapies for pathologic type 2 inflammation is opening a new approach to asthma treatment; however, not all asthmatics have type 2 airway inflammation, especially those with severe corticosteroid-refractory asthma. Much less is known about non-type 2 immunological mechanisms in asthma. In health, inflammation triggers resolution mechanisms that control immune (type 1 and type 2) responses and enable the restoration of tissue homeostasis. The resolution response is comprised of cellular and molecular events, including production of specialized pro-resolving mediators (SPMs). SPMs halt leukocyte recruitment, promote macrophage efferocytosis, and restore epithelial barrier integrity, all of which are critical to resolution of inflammation in the lungs. Here, we review recent insights into the disruption of these homeostatic mechanisms and their contributions to non-type 2 inflammation in severe asthma immunopathogenesis.
哮喘是一种高度流行的气道异质性炎症性疾病。并非所有患者对皮质类固醇的抗炎治疗都有反应，这导致严重哮喘的发病率显著增加。人们非常关注定义在哮喘中起作用的 2 型炎症的细胞和分子机制。针对病理性 2 型炎症的靶向治疗的发展为哮喘治疗开辟了一种新方法；然而，并非所有哮喘患者都有 2 型气道炎症，尤其是那些严重皮质类固醇难治性哮喘患者。关于哮喘中的非 2 型免疫机制，人们知之甚少。在健康状态下，炎症会引发一系列的解决机制，这些机制可以控制免疫（1 型和 2 型）反应，并使组织的内稳态得以恢复。该解决反应包括细胞和分子事件，其中包括产生专门的促解决介质（SPM）。SPM 可以阻止白细胞募集，促进巨噬细胞吞噬作用，并恢复上皮屏障完整性，所有这些对于肺部炎症的解决都是至关重要的。在这里，我们回顾了最近对这些内稳态机制的破坏及其对严重哮喘免疫发病机制中非 2 型炎症的影响的研究进展。
