IL-17A Is Elevated in End-Stage Chronic Obstructive Pulmonary Disease and Contributes to Cigarette Smoke-induced Lymphoid Neogenesis.
Am J Respir Crit Care Med
; 191(11): 1232-41, 2015 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-25844618
ABSTRACT
RATIONALE 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. OBJECTIVES:
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. MEASUREMENTS AND MAINRESULTS:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Fumar
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Interleucina-17
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Doença Pulmonar Obstrutiva Crônica
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Pulmão
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Tecido Linfoide
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article