IL-17RA Is Required for CCL2 Expression, Macrophage Recruitment, and Emphysema in Response to Cigarette Smoke

作者：Kong Chen, Derek Pociask, Jeremy P. McAleer, Yvonne R. Chan, John F. Alcorn, James L. Kreindler, Matthew R. Keyser, Steven D. Shapiro, A. McGarry Houghton, Jay K. Kolls, Mingquan Zheng · 发表于：PLoS ONE · 年份：2011 · DOI：10.1371/journal.pone.0020333 · 被引用次数：163 · 研究领域：Chronic Obstructive Pulmonary Disease (COPD) Research、Asthma and respiratory diseases、Pediatric health and respiratory diseases

Chronic Obstructive Pulmonary Disease (COPD) is characterized by airspace enlargement and peribronchial lymphoid follicles; however, the immunological mechanisms leading to these pathologic changes remain undefined. Here we show that cigarette smoke is a selective adjuvant that augments in vitro and in vivo Th17, but not Th1, cell differentiation via the aryl hydrocarbon receptor. Smoke exposed IL-17RA(-/-) mice failed to induce CCL2 and MMP12 compared to WT mice. Remarkably, in contrast to WT mice, IL-17RA(-/-) mice failed to develop emphysema after 6 months of cigarette smoke exposure. Taken together, these data demonstrate that cigarette smoke is a potent Th17 adjuvant and that IL-17RA signaling is required for chemokine expression necessary for MMP12 induction and tissue emphysema.