Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, Hamilton, Ontario, Canada.
Respir Res. 2012 Sep 19;13(1):81. doi: 10.1186/1465-9921-13-81.
Evidence suggests that dendritic cells accumulate in the lungs of COPD patients and correlate with disease severity. We investigated the importance of IL-1R1 and its ligands IL-1α and β to dendritic cell accumulation and maturation in response to cigarette smoke exposure.
Mice were exposed to cigarette smoke using a whole body smoke exposure system. IL-1R1-, TLR4-, and IL-1α-deficient mice, as well as anti-IL-1α and anti-IL-1β blocking antibodies were used to study the importance of IL-1R1 and TLR4 to dendritic cell accumulation and activation.
Acute and chronic cigarette smoke exposure led to increased frequency of lung dendritic cells. Accumulation and activation of dendritic cells was IL-1R1/IL-1α dependent, but TLR4- and IL-1β-independent. Corroborating the cellular data, expression of CCL20, a potent dendritic cells chemoattractant, was IL-1R1/IL-1α-dependent. Studies using IL-1R1 bone marrow-chimeric mice revealed the importance of IL-1R1 signaling on lung structural cells for CCL20 expression. Consistent with the importance of dendritic cells in T cell activation, we observed decreased CD4+ and CD8+ T cell activation in cigarette smoke-exposed IL-1R1-deficient mice.
Our findings convey the importance of IL-1R1/IL-1α to the recruitment and activation of dendritic cells in response to cigarette smoke exposure.
有证据表明，树突状细胞在 COPD 患者的肺部积聚，并与疾病严重程度相关。我们研究了 IL-1R1 及其配体 IL-1α 和β 对树突状细胞在香烟烟雾暴露下的积聚和成熟的重要性。
使用全身烟雾暴露系统使小鼠暴露于香烟烟雾中。使用 IL-1R1-、TLR4- 和 IL-1α 缺陷小鼠以及抗 IL-1α 和抗 IL-1β 阻断抗体来研究 IL-1R1 和 TLR4 对树突状细胞积聚和激活的重要性。
急性和慢性香烟烟雾暴露导致肺部树突状细胞频率增加。树突状细胞的积聚和激活依赖于 IL-1R1/IL-1α，但不依赖于 TLR4 和 IL-1β。与细胞数据一致，趋化因子 CCL20 的表达是 IL-1R1/IL-1α 依赖性的，CCL20 是一种有效的树突状细胞趋化因子。使用 IL-1R1 骨髓嵌合小鼠的研究表明，IL-1R1 信号对肺结构细胞 CCL20 表达的重要性。与树突状细胞在 T 细胞激活中的重要性一致，我们观察到在香烟烟雾暴露的 IL-1R1 缺陷小鼠中 CD4+和 CD8+T 细胞激活减少。
我们的研究结果表明，IL-1R1/IL-1α 对香烟烟雾暴露下树突状细胞的募集和激活至关重要。
