Abstract
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.
Highlights
Chronic obstructive pulmonary disease (COPD) accounts for 5– 10% of all deaths globally and it is estimated that 80 million people currently suffer with COPD of varying degrees [1]
The addition of 0.5% cigarette smoke extract (CSE) significantly increased the percentage of CD4 and CD8 T-cells that stained positive for IL-17 (Figure 1A)
IL-17 has been shown to be an important inducer of CCL2, and mice overexpressing IL-17A or IL-17F show elevated CCL2 in the lung
Summary
Chronic obstructive pulmonary disease (COPD) accounts for 5– 10% of all deaths globally and it is estimated that 80 million people currently suffer with COPD of varying degrees [1]. COPD is attributed to persistent exposure to noxious gases and particulates, and is most often associated with cigarette smoke. This exposure induces a chronic inflammatory state in which there is mucus hypersecretion and the formation of airway associated lymphoid follicles [1,2,3]. This leads to inflammatory obstruction of the upper and lower airways and destruction of parenchymal structure (emphysema), leading to chronic, progressive decrease in airflow [2,3]. IL-17 producing T cells known as Th17 cells have been identified in lungs from COPD patients [4,9], suggesting an important role for this cytokine
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