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. 2015 Jun 1;191(11):1232-41. doi: 10.1164/rccm.201410-1861OC.


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 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.

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.

Keywords: COPD; IL-17; chemokines; cytokines; lymphoid follicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • CXCL12 protein, human
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Interleukin-17