Preventative Tracheal Administration Of Interleukin-27 Attenuates Allergic Asthma By Improving The Lung Th1 Microenvironment

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.