Larose Marie-Chantal, Archambault Anne-Sophie, Provost Véronique, Laviolette Michel, Flamand Nicolas
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Département de Médecine, Université Laval, Québec City, QC, Canada.
Front Med (Lausanne). 2017 Aug 11;4:136. doi: 10.3389/fmed.2017.00136. eCollection 2017.
Asthma is an inflammatory disease usually characterized by increased Type 2 cytokines and by an infiltration of eosinophils to the airways. While the production of Type 2 cytokines has been associated with T2 lymphocytes, increasing evidence indicates that group 2 innate lymphoid cells (ILC2) play an important role in the production of the Type 2 cytokines interleukin (IL)-5 and IL-13, which likely amplifies the recruitment of eosinophils from the blood to the airways. In that regard, recent asthma treatments have been focusing on blocking Type 2 cytokines, notably IL-4, IL-5, and IL-13. These treatments mainly result in decreased blood or sputum eosinophil counts as well as decreased asthma symptoms. This supports that therapies blocking eosinophil recruitment and activation are valuable tools in the management of asthma and its severity. Herein, we review the mechanisms involved in eosinophil and ILC2 recruitment to the airways, with an emphasis on eotaxins, other chemokines as well as their receptors. We also discuss the involvement of other chemoattractants, notably the bioactive lipids 5-oxo-eicosatetraenoic acid, prostaglandin D, and 2-arachidonoyl-glycerol. Given that eosinophil biology differs between human and mice, we also highlight and discuss their responsiveness toward the different eosinophil chemoattractants.
哮喘是一种炎症性疾病,通常表现为2型细胞因子增加以及嗜酸性粒细胞浸润气道。虽然2型细胞因子的产生与T2淋巴细胞有关,但越来越多的证据表明,2型固有淋巴细胞(ILC2)在2型细胞因子白细胞介素(IL)-5和IL-13的产生中起重要作用,这可能会增强嗜酸性粒细胞从血液到气道的募集。在这方面,最近的哮喘治疗一直专注于阻断2型细胞因子,特别是IL-4、IL-5和IL-13。这些治疗主要导致血液或痰液中嗜酸性粒细胞计数减少以及哮喘症状减轻。这支持了阻断嗜酸性粒细胞募集和激活的疗法是管理哮喘及其严重程度的有价值工具。在此,我们综述了嗜酸性粒细胞和ILC2募集到气道的相关机制,重点关注嗜酸性粒细胞趋化因子、其他趋化因子及其受体。我们还讨论了其他趋化剂的作用,特别是生物活性脂质5-氧代-二十碳四烯酸、前列腺素D和2-花生四烯酰甘油。鉴于人类和小鼠的嗜酸性粒细胞生物学特性不同,我们还强调并讨论了它们对不同嗜酸性粒细胞趋化剂的反应性。