STING通路的活化诱导巨噬细胞极化促进T细胞免疫应答  

M1 polarization of macrophage induced by STING signaling promotes T cell immune response

作　　者：李健飞 段植 刘倩 宗启印 段婉露 刘付婷 张浩[1] 周强[1] 王琴[1] Li Jianfei;Duan Zhi;Liu Qian;Zong Qiyin;Duan Wanlu;Liu Futing;Zhang Hao;Zhou Qiang;Wang Qin(Dept of Clinical Laboratory,The Second Affiliated Hospital of Anhui Medical University,Hefei230601)

机构地区：[1]安徽医科大学第二附属医院检验科,合肥230601

出　　处：《安徽医科大学学报》2024年第11期1974-1981,共8页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金项目(编号:81902056);安徽省高校科研计划重点项目(编号:2023AH053169)。

摘　　要：目的探讨干扰素基因刺激因子(STING)通路的活化对巨噬细胞极化功能的影响,及其对T细胞应答的作用。方法利用小鼠RAW264.7巨噬细胞系,给予STING激动剂二聚氨基苯并咪唑(diABZI)刺激,Western blot检测巨噬细胞STING通路相关蛋白表达,包括TANK结合激酶1(TBK1)、干扰素调节因子3(IRF3)、STING、p-TBK1、p-IRF3、p-STING;流式细胞术检测巨噬细胞极化表型;STING通路活化后的巨噬细胞与T细胞共培养,流式分析T细胞表型及功能变化。结果diABZI刺激巨噬细胞3 h后,STING通路活化相关蛋白显著上调,刺激12 h后巨噬细胞表面CD86表达上调,CD86/CD206比值升高,呈现M1极化表型。STING通路活化诱导极化的巨噬细胞与T淋巴细胞共培养,CD8^(+)T细胞分泌细胞因子能力增强,并且CD107a表达上调;同时,CD4^(+)T细胞细胞因子分泌增强。结论STING通路活化诱导巨噬细胞M1极化,促进T细胞功能增强,尤其是CD8^(+)T细胞的免疫应答。Objective To investigate the effect of activation of the stimulator of interferon genes(STING)pathway on macrophage polarization function and its role in T-cell response.Methods Mouse macrophage RAW264.7 cells were used.STING signaling related proteins in RAW264.7 macrophage treated with STING agonist diABZI were analyzed by Western blot,including TANK-binding kinase-l(TBK1),interferon regulatory factor-3(IRF3),STING,p-TBK1,p-IRF3,p-STING.The polarization of macrophage RAW264.7 cells treated with diABZI was analyzed by flow cytometry.Co-culture of diABZI-treated RAW264.7 macrophage and T cells was applied to evaluate the change of T cell response.Results STING signaling related proteins were upregulated in macrophage RAW264.7 cells treated with diABZI for 3 hours.The expression of CD86 was upregulated on the surface of macrophages after 12 hours of diABZI treatment,and the CD86/CD206 ratio was elevated,which presented the M1 polarization phenotype.When coculturing diABZI-treated macrophage RAW264.7 cells with T cells,the cytokine secretion ability of T cells including CD4^(+)T and CD8^(+)T cells was enhanced and the expression of CD107a in CD8^(+)T cells was upregulated.Conclusion STING signaling induces M1 polarization of macrophages which enhance the function of T cells,especially CD8^(+)T cell immune response.

关 键 词：巨噬细胞 STING通路 巨噬细胞极化 T细胞免疫应答 CD4^(+)T细胞 CD8^(+)T细胞 

分 类 号：R392.12[医药卫生—免疫学]