Premium
Preventative tracheal administration of interleukin‐27 attenuates allergic asthma by improving the lung Th1 microenvironment
Author(s) -
Liu Xiaojing,
Li Shanqun,
Jin Jianjun,
Zhu Tao,
Xu Kan,
Liu Cheng,
Zeng Yuzhen,
Mao Ruolin,
Wang Xiangdong,
Chen Zhihong
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27422
Subject(s) - immunology , stat4 , stat6 , chemokine , stat protein , medicine , monocyte , t cell , dendritic cell , signal transduction , cancer research , stat3 , interleukin 4 , cytokine , inflammation , biology , immune system , stat , microbiology and biotechnology
Background: Interleukin‐27 (IL‐27) modulates CD4+ T‐cell differentiation and function. The aim of this study is to investigate the effect and molecular mechanisms of IL‐27 on the development of asthma. Methods: IL‐27 was intranasally administered in an ovalbumin‐induced asthma model, and lung mononuclear cells and different Th cell classes were detected by fluorescence‐activated cell sorting. The effect and mechanisms of IL‐27 on human bronchial epithelial (HBE) cells were investigated by measuring changes in chemotactic factors, cytokines, transcription factors, and signaling pathways. Results: We found that intranasal administration of IL‐27 could attenuate airway inflammation and hyperresponsiveness, upregulate the type 1 T helper (Th1)‐T memory (Tm) cells and regulatory T (Treg) cells subgroups of lung tissue lymphocytes, and diminish the levels of type 2 T helper (Th2) cytokines. IL‐27 upregulated the expression of C‐C motif chemokine ligand 2 (CCL2), CCL3, and CCL4 in HBE cells and promoted the production of chemotactic factors to attract monocyte recruitment. Recruited monocytes secondarily secreted IL‐27 to influence HBE cells in a positive feedback cycle. After IL‐27 intervention, signal transducer and activator of transcription 1 (STAT1) phosphorylation increased, while STAT4 and STAT6 phosphorylation declined. Conclusions: Preventative intranasal administration of IL‐27 can recruit more IL‐27‐secreted monocytes to the airway and change the different T‐cell classes in lung. The improved Th1 environment helps to alleviate Th2‐mediated allergic asthma by repairing the STAT1 pathway but not the STAT4 pathway.