痤疮丙酸杆菌通过促进Th1细胞和Th17细胞的分化诱发肉芽肿形成  

Propionibacterium acnes induces the formation of granulomas via promoting Th1 and Th17 cell differentiation

作　　者：葛丽艳[1,2] 田洁[1] 汤新逸[1] 耿丽娜[1] 杨珺[1] 许化溪[1] 王胜军[1,2] 仝佳[1,2] 

机构地区：[1]江苏大学检验医学研究所,江苏镇江212013 [2]江苏大学附属人民医院,江苏镇江212002

出　　处：《细胞与分子免疫学杂志》2015年第11期1447-1451,1457,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81101227);高级人才专项资助(11JDG127);镇江市社会发展科技支撑计划(SH2014042)

摘　　要：目的研究痤疮丙酸杆菌(P.acnes)在树突状细胞成熟、辅助性T(Th)细胞亚群分化过程中的免疫刺激作用,进而探讨其诱发肉芽肿的可能机制。方法以P.acnes刺激小鼠骨髓源性树突状细胞(BMDC),流式细胞术检测其表面共刺激分子(CD40、CD80、CD86)和主要组织相容性复合体Ⅱ(MHCⅡ)的变化,实时荧光定量PCR(qRT-PCR)检测白细胞介素12(IL-12)、IL-6和IL-23的mRNA水平,ELISA检测上清中IL-12、IL-6和IL-23的蛋白浓度;P.acnes与BMDC、CD4^+T细胞共培养,流式细胞术检测Th1细胞、Th17细胞分化情况;小鼠尾静脉注射加热灭活的P.acnes,建立肝脏肉芽肿模型,并通过qRT-PCR检测肝脏组织中IL-17、γ干扰素(IFN-γ)的mRNA水平。结果经P.acnes作用后,BMDC表面CD40、CD80、CD86和MHCⅡ分子的表达增强,上清中IL-12、IL-6和IL-23的水平增高,促进CD4^+T细胞向Th1细胞、Th17细胞分化;P.acnes诱导建立的肝脏肉芽肿中,IL-17和IFN-γ的mRNA表达增强。结论 P.acnes可通过活化BMDC,促进Th1细胞、Th17细胞的分化,进而导致炎性肉芽肿形成。Objective To investigate the immunostimulatory role of Propionibacterium acnes （P. aches） in the differentiation of dendritic cell maturation and T helper （Th） subsets, and further explore the potential mechanism of its granuloma-inducing effect. Methods After the mouse bone marrow-derived dendritic cells （BMDCs） were stimulated by P. acnes, the expressions of co-stimulatory molecules CD40, CD80, CD86 and major histocompatibility complex Ⅱ （ MHC Ⅱ） on BMDCs were detected by flow cytometry, the mRNA levels of inflammatory cytokines IL-12, IL-6 and IL-23 were measured by real-time quantitative PCR （qRT-PCR）, and the protein concentrations of corresponding cytokines were analyzed by ELISA. Thereafter, BMDCs were cultured in the presence of P. acnes and CD4 ^＋ T cells, and the percentages of Th1 and Th17 cells were detected by flow cytometry. In addition, murine model of liver granuloma was constructed by injecting heat-killed P. acnes through tail vein, and the mRNA levels of IL-17 and IFN-γ were measured by qRT-PCR. Results P. acnes up-regulated the expressions of CD40, CD80, CD86 and MHC Ⅱon BMDCs, and the mRNA and protein levels of the IL-12, IL-6 and IL-23 cytokines were also higher on P. acnes-treated BMDCs compared with non-stimulated BMDCs. Furthermore, the percentages of Th1 and Th17 cells in the co-culture system increased. In addition, the mRNA levels of IL-17 and IFN-γ were elevated obviously in the liver with abundant granulomas after P. aches treatment. Conclusion P. acnes could activate BMDCs, promote the differentiation of Th1 and Th17 cells, and further induce the formation of granulomas.

关 键 词：痤疮丙酸杆菌 树突状细胞 肉芽肿 辅助性T细胞 

分 类 号：R392.12[医药卫生—免疫学] R758.733[医药卫生—基础医学]