title: Tc17 cells are associated with cigarette smoke-induced lung inflammation and emphysema.
abstract: OBJECTIVE
  Some types of T lymphocytes, especially cytotoxic T-cells (Tc1) and T-helper (Th17) cells, play a pivotal role in cigarette smoke-induced lung diseases. However, whether Tc17 cells are involved remains largely unknown. We investigated Tc17 involvement using a cigarette smoke-exposure model.
  
  
  METHODS
  Groups of mice were exposed to cigarette smoke or filtered air. At weeks 2, 8, 12 and 24, mice were sacrificed to observe histological changes by HE stain and/or immunohistochemical staining. The frequency of T cell subsets in the lung and spleen were detected by flow cytometry. In addition, the expression levels of T cell-related factors were measured by real-time polymerase chain reaction or enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Cigarette smoke caused substantial inflammatory cell infiltration and led to emphysema. Cigarette smoke exposure promoted the expression of interferon-gamma (IFN)-γ and interleukin (IL)-17A at the messenger ribonucleic acid and protein levels. In addition to Tc1 and Th17 cells, pulmonary and splenic Tc17 cells increased, which was accompanied by the upregulation of cytokines IL-6, transforming growth factor beta (TGF)-β) and transcriptional factors Stat3 and RAR-related orphan receptor gamma. Compared with untreated mice, γH2AX-positive cells were more frequently observed in mice exposed to cigarette smoke.
  
  
  CONCLUSIONS
  Long-term cigarette smoke exposure induced Tc17 cell expansion both locally and distally, which was associated with emphysema and deoxyribonucleic acid damage. As an important source of IL-17A, this T cell subset may be a potential target for chronic obstructive pulmonary disease therapy.
authors: Department of Respiratory and Critical Care Medicine, Second Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors: Hongbin
authors: H
authors: Zhou
authors: Wen
authors: W
authors: Hua
authors: Yan
authors: Y
authors: Jin
authors: Chao
authors: C
authors: Zhang
authors: Luanqing
authors: L
authors: Che
authors: Lixia
authors: L
authors: Xia
authors: Jiesen
authors: J
authors: Zhou
authors: Zhihua
authors: Z
authors: Chen
authors: Wen
authors: W
authors: Li
authors: Huahao
authors: H
authors: Shen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011656:Pulmonary Emphysema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*; D058504:Th17 Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D007371:Interferon-gamma
keywords: DNA damage; Tc17; cigarette smoke; emphysema; inflammation