Department of Medicine, University of California San Diego.
Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Curr Opin Allergy Clin Immunol. 2021 Feb 1;21(1):65-70. doi: 10.1097/ACI.0000000000000712.
The purpose of this review is to summarize the complex cellular interactions of aspirin-exacerbated respiratory disease (AERD) and how these interactions promote pathogenic mechanisms of AERD.
In addition to characteristic changes in eicosanoid levels, recent studies have identified increases in alarmin cytokines (IL-33, thymic stromal lymphopoietin) as well as activated innate lymphoid and plasma cell populations in samples from AERD patients.
Patients with AERD typically demonstrate high levels of proinflammatory eicosanoids including cysteinyl leukotrienes (CysLTs) and prostaglandin D2 (PGD2) and hyporesponsiveness to prostaglandin E2 (PGE2). CysLTs are released by mast cells, eosinophils, and adherent platelets and promote epithelial release of IL-33, which activates mast cells and group 2 innate lymphoid cells (ILC2s) in concert with CysLTs. TSLP induces PGD2 release from mast cells which activates and recruits eosinophils, basophils, Th2 cells, and ILC2s via CRTH2. In turn, ILC2s and other cell types produce Th2 cytokines IL-4, IL-5, and IL-13 that, along with CysLTs and PGD2, promote bronchoconstriction, eosinophilic tissue inflammation, and mucus production.
本文旨在总结阿司匹林加重性呼吸系统疾病（AERD）中复杂的细胞间相互作用，以及这些相互作用如何促进 AERD 的发病机制。
除了花生四烯酸代谢产物水平的特征性变化外，最近的研究还发现 AERD 患者样本中警报素细胞因子（IL-33、胸腺基质淋巴细胞生成素）和活化的固有淋巴细胞和浆细胞群体增加。
AERD 患者通常表现出高水平的促炎类花生酸，包括半胱氨酰白三烯（CysLTs）和前列腺素 D2（PGD2），并且对前列腺素 E2（PGE2）的反应降低。CysLTs 由肥大细胞、嗜酸性粒细胞和黏附血小板释放，并促进上皮细胞释放 IL-33，与 CysLTs 一起激活肥大细胞和 2 型固有淋巴细胞（ILC2）。TSLP 诱导肥大细胞释放 PGD2，激活并募集嗜酸性粒细胞、嗜碱性粒细胞、Th2 细胞和 ILC2 通过 CRTH2。反过来，ILC2 和其他细胞类型产生 Th2 细胞因子 IL-4、IL-5 和 IL-13，与 CysLTs 和 PGD2 一起促进支气管收缩、嗜酸性粒细胞组织炎症和黏液产生。
