IL-17RA is required for CCL2 expression, macrophage recruitment, and emphysema in response to cigarette smoke.
oleh: Kong Chen, Derek A 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
| Format: | Article |
|---|---|
| Diterbitkan: | Public Library of Science (PLoS) 2011-01-01 |
Deskripsi
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.