title: IL-17A Is Elevated in End-Stage Chronic Obstructive Pulmonary Disease and Contributes to Cigarette Smoke-induced Lymphoid Neogenesis.
abstract: BACKGROUND
  End-stage chronic obstructive pulmonary disease (COPD) is associated with an accumulation of pulmonary lymphoid follicles. IL-17A is implicated in COPD and pulmonary lymphoid neogenesis in response to microbial stimuli. We hypothesized that IL-17A is increased in peripheral lung tissue during end-stage COPD and also directly contributes to cigarette smoke-induced lymphoid neogenesis.
  
  
  OBJECTIVE
  To characterize the tissue expression and functional role of IL-17A in end-stage COPD.
  
  
  METHODS
  Automated immune detection of IL-17A and IL-17F was performed in lung tissue specimens collected from patients with Global Initiative for Chronic Obstructive Lung Disease stage I-IV COPD, and smoking and never-smoking control subjects. In parallel, Il17a(-/-) mice and wild-type control animals were exposed to cigarette smoke for 24 weeks, and pulmonary lymphoid neogenesis was assessed.
  
  
  RESULTS
  Tissue expression of IL-17A and IL-17F was increased in COPD and correlated with lung function decline. IL-17A was significantly elevated in severe to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease III/IV) compared with both smokers and never-smokers without COPD. Although CD3(+) T cells expressed IL-17A in very severe COPD, most IL-17A(+) cells were identified as tryptase-positive mast cells. Attenuated lymphoid neogenesis and reduced expression of the B-cell attracting chemokine C-X-C motif ligand (CXCL) 12 was observed in cigarette smoke-exposed Il17a(-/-) mice. CXCL12 was also highly expressed in lymphoid follicles in COPD lungs, and the pulmonary expression was significantly elevated in end-stage COPD.
  
  
  CONCLUSIONS
  IL-17A in the peripheral lung of patients with severe to very severe COPD may contribute to disease progression and development of lymphoid follicles via activation of CXCL12.
authors.affiliation: 1 Department of Experimental Medical Science and.
authors.forename: Abraham B
authors.initials: AB
authors.lastname: Roos
authors.forename: Caroline
authors.initials: C
authors.lastname: Sandén
authors.forename: Michiko
authors.initials: M
authors.lastname: Mori
authors.forename: Leif
authors.initials: L
authors.lastname: Bjermer
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stampfli
authors.forename: Jonas S
authors.initials: JS
authors.lastname: Erjefält
mesh_terms: D000368:Aged; D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D008168:Lung / Q000473:pathology*; D008221:Lymphoid Tissue / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000473:pathology*; D012907:Smoking / Q000009:adverse effects*
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D020381:Interleukin-17
keywords: COPD; IL-17; chemokines; cytokines; lymphoid follicles