TY - JOUR T1 - Lung Myeloid Dendritic Cells Coordinately Induce T<sub>H</sub>1 and T<sub>H</sub>17 Responses in Human Emphysema JF - Science Translational Medicine SP - 4ra10 LP - 4ra10 DO - 10.1126/scitranlsmed.3000154 VL - 1 IS - 4 AU - Shan, Ming AU - Cheng, Han-Fang AU - Song, Li-zhen AU - Roberts, Luz AU - Green, Linda AU - Hacken-Bitar, Joan AU - Huh, Joseph AU - Bakaeen, Faisal AU - Coxson, Harvey O. AU - Storness-Bliss, Claudine AU - Ramchandani, Mahesh AU - Lee, Seung-Hyo AU - Corry, David B. AU - Kheradmand, Farrah Y1 - 2009/10/28 UR - http://stm.sciencemag.org/content/1/4/4ra10.abstract N2 - Exposure to tobacco smoke activates innate and adaptive immune responses that in long-term smokers have been linked to diseases of the lungs, cardiovascular system, joints, and other organs. The destruction of lung tissue that underlies smoking-induced emphysema has been associated with T helper 1 cells that recognize the matrix protein elastin. Factors that result in the development of such autoreactive T cells in smokers remain unknown but are crucial for further understanding the pathogenesis of systemic inflammatory diseases in smokers. Here, we show that lung myeloid dendritic cells were sufficient to induce T helper 1 and T helper 17 responses in CD4 T cells. T helper 1 and 17 cells are invariably present in lungs from patients with emphysema but not in lungs from normal individuals. Interleukin-17A, a canonical T helper 17 cytokine, enhanced secretion of CCL20, a chemoattractant for dendritic cells, and matrix metalloproteinase 12, a potent elastolytic proteinase, from lung macrophages. Thus, although diverse lung factors potentially contribute to T helper effector differentiation in vivo, lung myeloid dendritic cells direct the generation of pathogenic T cells and support a feedback mechanism that sustains both inflammatory cell recruitment and lung destruction. This mechanism may underlie disease in other elastin-rich organs and tissues. Copyright © 2009, American Association for the Advancement of Science ER -