Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 52, Issue 2, Pages 222-236Publisher
WILEY
DOI: 10.1002/eji.202049076
Keywords
CD8(+)T cells; Emphysema; IFN-gamma; IL-27; Smoke
Categories
Funding
- National Natural Science Foundation of China [81860009, 81800037]
- Medical Excellence Award - Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University
- second batch of Guangxi medical high-level talents and 139 plan in 2019 [G201903035]
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The research reveals that IL-27 plays a negative regulatory role in chronic inflammation induced by smoking, preventing CD8(+)T cells from producing excessive inflammatory responses. This study provides a new therapeutic strategy for smoking-related COPD/emphysema by targeting the IL-27 pathway.
Chronic airway inflammation mediated by CD8(+)T lymphocytes contributes to the pathogenesis of Chronic obstructive pulmonary disease (COPD). Deciphering the fingerprint of the chronic inflammation orchestrated by CD8(+)T cells may allow the development of novel approaches to COPD management. Here, the expression of IL-27 and IFN-gamma(+)CD8(+)Tc1 cells were evaluated in patients with COPD and in cigarette smoke-exposed mice. The production of IL-27 by marrow-derived dendritic cells (mDCs) in response to cigarette smoke extract (CSE) was assessed. The role of IL-27 in IFN-gamma(+)CD8(+)Tc1 cells was explored. We demonstrated that elevated IL-27 was accompanied by an exaggerated IFN-gamma(+)CD8(+)Tc1 response in a smoking mouse model of emphysema. We noted that lung dendritic cells were one of the main sources of IL-27 during chronic cigarette smoke exposure. Moreover, CSE directly induced the production of IL-27 by mDCs in vitro. IL-27 negatively regulated the differentiation of IFN-gamma(+)CD8(+)Tc1 cells isolated from cigarette smoke-exposed mice in a STAT1- and STAT3-independent manner. Systemic administration of recombinant IL-27 attenuated IFN-gamma(+)CD8(+)Tc1 response in the late phase of cigarette smoke exposure. Our results uncovered that IL-27 negatively regulates IFN-gamma(+)CD8(+)Tc1 response in the late stage of chronic cigarette smoke exposure, which may provide a new strategy for the anti-inflammatory treatment of smoking-related COPD/emphysema.
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