Lung myeloid dendritic cells coordinately induce TH1 and TH17 responses in human emphysema.
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.
Shan
Ming
M
Department of Medicine, Section of Pulmonary and Critical Care, Baylor College of Medicine, Houston, TX 77030, USA.
Cheng
Han-Fang
HF
Song
Li-Zhen
LZ
Roberts
Luz
L
Green
Linda
L
Hacken-Bitar
Joan
J
Huh
Joseph
J
Bakaeen
Faisal
F
Coxson
Harvey O
HO
Storness-Bliss
Claudine
C
Ramchandani
Mahesh
M
Lee
Seung-Hyo
SH
Corry
David B
DB
Kheradmand
Farrah
F
D000938:Antigen-Presenting Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004646:Emphysema / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008168:Lung / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*