IL-17A Is Elevated in End-Stage Chronic Obstructive Pulmonary Disease and Contributes to Cigarette Smoke-induced Lymphoid Neogenesis

• Published in: American journal of respiratory and critical care medicine 2015-06, Vol.191 (11), p.1232-1241
• Main Authors: Roos, Abraham B, Sandén, Caroline, Mori, Michiko, Bjermer, Leif, Stampfli, Martin R, Erjefält, Jonas S
• Format: Article
• Language: English
• Subjects: Aged; Animals; Chemokine CXCL12 - metabolism; Disease Models, Animal; Disease Progression; Female; Humans; Interleukin-17 - immunology; Lung - pathology; Lymphoid Tissue - metabolism; Lymphoid Tissue - pathology; Male; Mice; Mice, Inbred C57BL; Middle Aged; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Disease, Chronic Obstructive - pathology; Smoking - adverse effects
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201410-1861oc

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. To characterize the tissue expression and functional role of IL-17A in end-stage COPD. 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. 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. 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.