IL‐27 mediates anti‐inflammatory effect in cigarette smoke induced emphysema by negatively regulating IFN‐γ producing cytotoxic CD8 + T cells in mice

Autor: Tao Feng, Qi-xiang Sun, Shi-Lin Qiu, Zai-qing He, Min-chao Duan, Fu-shou Chen, Jian-peng Zhou, Yan-qiong Chen, Hai-juan Tang, Hua-jiao Qin
Rok vydání: 2021
Předmět:
Zdroj: European Journal of Immunology. 52:222-236
ISSN: 1521-4141
0014-2980
DOI: 10.1002/eji.202049076
Popis: 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-γ+ 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-γ+ CD8+ Tc1 cells was explored. We demonstrated that elevated IL-27 was accompanied by an exaggerated IFN-γ+ 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-γ+ CD8+ Tc1 cells isolated from cigarette smoke-exposed mice in a STAT1- and STAT3-independent manner. Systemic administration of recombinant IL-27 attenuated IFN-γ+ CD8+ Tc1 response in the late phase of cigarette smoke exposure. Our results uncovered that IL-27 negatively regulates IFN-γ+ 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.
Databáze: OpenAIRE
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