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IL-17A Is Elevated in End-Stage Chronic Obstructive Pulmonary Disease and Contributes to Cigarette Smoke-induced Lymphoid Neogenesis.
- Source :
-
American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2015 Jun 01; Vol. 191 (11), pp. 1232-41. - Publication Year :
- 2015
-
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.<br />Objectives: To characterize the tissue expression and functional role of IL-17A in end-stage COPD.<br />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.<br />Measurements and Main 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.<br />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.
- Subjects :
- Aged
Animals
Chemokine CXCL12 metabolism
Disease Models, Animal
Disease Progression
Female
Humans
Male
Mice
Mice, Inbred C57BL
Middle Aged
Interleukin-17 immunology
Lung pathology
Lymphoid Tissue metabolism
Lymphoid Tissue pathology
Pulmonary Disease, Chronic Obstructive immunology
Pulmonary Disease, Chronic Obstructive pathology
Smoking adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1535-4970
- Volume :
- 191
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- American journal of respiratory and critical care medicine
- Publication Type :
- Academic Journal
- Accession number :
- 25844618
- Full Text :
- https://doi.org/10.1164/rccm.201410-1861OC