Objective To investigate the effect of interleukin(IL)-33 mediated macrophage polarization on the imbalance of regulatory T cells(Treg)/helper T cell-17(Th17)in non-small cell lung cancer(NSCLC).Methods The study enrolled 42 NSCLC inpatients(NSCLC group),40 healthy subjects(control group)admitted to the Fourth Clinical Medical College of Xinjiang Medical University from September 2020 to August 2021 as the study subjects.Th17,Treg and macrophages/monocytes in peripheral blood of the two groups were detected by flow cytometry.Magnetic beads were used to separate peripheral blood mononuclear cells from the NSCLC group and CD4+T cells from the control group,and IL-33 was used to induce macrophage polarization.The NSCLC macrophages treated with or without IL-33 were co-cultured with CD4+T cells.The mRNA levels of IL-10,TNF-α,IL-1 β,TGF-β,RORγt and FOXP3 were detected by RT-qPCR.Contents of TNF-α,1L-1 β,IL-10 and TGF-β in supernatant of cell culture were detected by CBA multi-factor kit.Results The levels of CD14+CD68+CD86+CD206-M1 and CD14+CD68+CD86-CD206+M2 macrophages and the ratio of CD14+CD68+CD86-CD206+M2/CD14+CD68+CD86+CD206-M1 in peripheral blood of NSCLC group were higher than those in the control group(P all＜0.05).In addition,the level of Treg and the ratio of Treg/Th17 in NSCLC group were higher than those in the control group(P all＜0.05).The concentration of IL-10 mRNA and TGF-β mRNA increased in the supernatant of macrophages induced by IL-33(P all＜0.05).FOXP3 mRNA level of M2 type macrophages co-cultured with CD4+T cells was significantly higher than that of M0 and M1 co-cultured groups(P＜0.05).Conclusion IL-33 can promote M2 polarization of macrophages in NSCLC,and M2 macrophages promote an increase in Treg/Th17 ratio,upregulating the Treg specific transcription factor FOXP3.This mechanism may be related to its promotion of increased IL-10 and TGF-β secretion.
关键词
非小细胞肺癌/巨噬细胞/白细胞介素-33/调节性T细胞/辅助性T细胞17
Key words
non-small cell lung cancer/macrophages/interleukin-33/regulatory T cells/helper T cell-17
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