Laboratory of Immunoregulation, VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Laboratory of Immunoregulation, VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
Immunity. 2019 Apr 16;50(4):975-991. doi: 10.1016/j.immuni.2019.03.018.
Asthma is a chronic inflammatory airway disease associated with type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-13, which promote airway eosinophilia, mucus overproduction, bronchial hyperresponsiveness (BHR), and immunogloubulin E (IgE) synthesis. However, only half of asthma patients exhibit signs of an exacerbated Type 2 response. "Type 2-low" asthma has different immune features: airway neutrophilia, obesity-related systemic inflammation, or in some cases, few signs of immune activation. Here, we review the cytokine networks driving asthma, placing these in cellular context and incorporating insights from cytokine-targeting therapies in the clinic. We discuss established and emerging paradigms in the context of the growing appreciation of disease heterogeneity and argue that the development of new and improved therapeutics will require understanding the diverse mechanisms underlying the spectrum of asthma pathologies.
哮喘是一种慢性炎症性气道疾病,与 2 型细胞因子白细胞介素-4(IL-4)、IL-5 和 IL-13 相关,这些细胞因子促进气道嗜酸性粒细胞增多、黏液过度产生、支气管高反应性(BHR)和免疫球蛋白 E(IgE)合成。然而,只有一半的哮喘患者表现出 2 型反应加剧的迹象。“2 型低”哮喘具有不同的免疫特征:气道中性粒细胞增多、肥胖相关的全身炎症,或在某些情况下,免疫激活的迹象很少。在这里,我们回顾了驱动哮喘的细胞因子网络,将这些网络置于细胞环境中,并结合临床中细胞因子靶向治疗的见解。我们将在不断增加的疾病异质性认识的背景下讨论既定和新兴的范例,并认为开发新的和改进的治疗方法将需要了解哮喘病理谱背后的各种机制。