Institute of Lung Health, Department of Infection, Inflammation and Immunity, University of Leicester, Leicester, LE3 9QP, England.
Chest. 2010 Apr;137(4):797-804. doi: 10.1378/chest.09-1839. Epub 2010 Feb 5.
The costimulatory molecule OX40 and its ligand, OX40L, mediate key aspects of allergic airway inflammation in animal models of asthma, including eosinophilic airway inflammation, airway hyperresponsiveness, and T helper 2 polarization. We sought to examine OX40/OX40L and interleukin (IL)-4 expression in asthma across severities.
Bronchial biopsies were obtained from 27 subjects with asthma (mild Global Initiative for Asthma [GINA] 1 [n = 10], moderate GINA 2-3 [n = 7], and severe GINA 4-5 [n = 10]) and 13 healthy controls. The number of OX40(+), OX40L(+), IL-4(+), and IL-4 receptor alpha (IL-4Ralpha)(+) cells in the lamina propria and airway smooth muscle (ASM) bundle and the intensity of IL-4Ralpha(+) expression by the ASM were assessed.
The number of OX40(+), OX40L(+), and IL-4(+) cells in the lamina propria and OX40(+) and IL-4(+) cells in the ASM bundle was significantly increased in subjects with mild asthma, but not in those with moderate or severe asthma, compared with healthy controls. In the subjects with asthma, OX40/OX40L expression was positively correlated with the number of eosinophils and IL-4(+) cells in the lamina propria. The number of IL-4Ralpha(+) cells in the lamina propria was significantly increased in moderate-to-severe disease, but not in mild asthma, compared with controls. IL-4Ralpha expression by the ASM bundle was not different among groups.
OX40/OX40L expression is increased in the bronchial submucosa in mild asthma, but not in moderate-to-severe disease, and is related to the degree of tissue eosinophilia and IL-4 expression. Whether these costimulatory molecules have a role as targets for asthma requires further investigation.
共刺激分子 OX40 和其配体 OX40L 在哮喘动物模型的过敏气道炎症的多个方面发挥重要作用，包括嗜酸性气道炎症、气道高反应性和 Th2 极化。我们试图在哮喘严重程度上检查 OX40/OX40L 和白细胞介素（IL）-4 的表达。
从 27 名哮喘患者（轻度全球哮喘倡议[GINA] 1 [n = 10]、中度 GINA 2-3 [n = 7]和重度 GINA 4-5 [n = 10]）和 13 名健康对照者中获取支气管活检标本。评估固有层和气道平滑肌（ASM）束中的 OX40(+)、OX40L(+)、IL-4(+)和 IL-4 受体 alpha（IL-4Ralpha)(+)细胞的数量，以及 ASM 中 IL-4Ralpha(+)表达的强度。
与健康对照组相比，轻度哮喘患者固有层中 OX40(+)、OX40L(+)和 IL-4(+)细胞以及 ASM 束中的 OX40(+)和 IL-4(+)细胞的数量显著增加，但在中度或重度哮喘患者中则没有。在哮喘患者中，OX40/OX40L 表达与固有层中嗜酸性粒细胞和 IL-4(+)细胞的数量呈正相关。与对照组相比，中重度疾病固有层中 IL-4Ralpha(+)细胞的数量显著增加，但在轻度哮喘患者中则没有。各组间 ASM 束中 IL-4Ralpha 表达无差异。
在轻度哮喘中，支气管粘膜下层中的 OX40/OX40L 表达增加，但在中重度疾病中则没有，并且与组织嗜酸性粒细胞和 IL-4 表达的程度相关。这些共刺激分子是否作为哮喘的靶点具有作用，尚需进一步研究。
