p204 is a member of the interferon-inducible p200 family proteins in mice.The p200 family has been reported to be multifunctional regulators of cell proliferation,differentiation,apoptosis and senescence.Interferon-in...p204 is a member of the interferon-inducible p200 family proteins in mice.The p200 family has been reported to be multifunctional regulators of cell proliferation,differentiation,apoptosis and senescence.Interferon-inducible protein 16(IFI16)is regarded as the human ortholog of p204 in several studies.This is possibly due to the similarity of their structures.However the consistency of their functions is still elusive.Currently,an emerging focus has been placed upon the role of the p200 proteins as sensors for microbial DNA in innate immune responses and provides new insights into infections as well as autoimmune diseases.This review specially focuses on IFI16 and p204,the member of p200 family in human and murine respectively,and their pathophysiological roles in innate immune responses,cell differentiation and proliferation.展开更多
Interferon gamma-inducible protein 16(IFI16)senses DNA in the cytoplasm and the nucleus by using two tandem hematopoietic interferon-inducible nuclear(HIN)domains,HINa and HINb,through the cooperative assembly of IFI1...Interferon gamma-inducible protein 16(IFI16)senses DNA in the cytoplasm and the nucleus by using two tandem hematopoietic interferon-inducible nuclear(HIN)domains,HINa and HINb,through the cooperative assembly of IFI16 filaments on double-stranded DNA(dsDNA).The role of HINa in sensing DNA is not clearly understood.Here,we describe the crystal structure of the HINa domain in complex with DNA at 2.55A°resolution and provide the first insight into the mode of DNA binding by the HINa domain.The structure reveals the presence of two oligosaccharide/nucleotide-binding(OB)folds with a unique DNA-binding surface.HINa uses loop L45 of the canonical OB2 fold to bind to the DNA backbone.The dsDNA is recognized as two single strands of DNA.Interestingly,deletion of HINb compromises the ability of IFI16 to induce IFN-b,while HINa mutants impaired in DNAbinding enhance the production of IFN-b.These results shed light on the roles of IFI16 HIN domains in DNA recognition and innate immune responses.展开更多
目的研究干扰素诱导蛋白16(interferon inducible protein 16,IFI16)在银屑病中的表达及分布,探讨其在银屑病发病中的作用。方法采用RT-PCR、免疫组化的方法分别检测10例银屑病患者皮损和10例健康人皮肤组织真皮与表皮中IFI16的表达情况...目的研究干扰素诱导蛋白16(interferon inducible protein 16,IFI16)在银屑病中的表达及分布,探讨其在银屑病发病中的作用。方法采用RT-PCR、免疫组化的方法分别检测10例银屑病患者皮损和10例健康人皮肤组织真皮与表皮中IFI16的表达情况;采用RT-PCR、Western印记方法检测IFN-γ,TNF-α,IL-17刺激前后Ha Ca T细胞中IFI16的表达情况。结果银屑病患者皮损处IFI16的表达明显高于健康人皮肤,并且以表皮表达为主,免疫组化结果显示IFI16主要定位于银屑病患者的角质形成细胞中。银屑病相关细胞因子IFN-γ,TNF-α和IL-17可以上调角质形成细胞中IFI16的表达水平。结论IFI16在银屑病患者皮损处表达明显高于正常人皮肤,并且IFN-γ,TNF-α和IL-17可以诱导其表达上调,可能是银屑病角质形成细胞的活化机制之一。展开更多
目的研究黄芪多糖(APS)对人外周血单核细胞(PBMC)源性树突状细胞(DCs)的基因表达和其功能变化的影响,进一步探讨黄芪多糖的抗AS的作用机制。方法以健康人外周血分离PBMC源性DCs和血清作为研究对象,培育5 d后,随机分为APS组和对照组。其...目的研究黄芪多糖(APS)对人外周血单核细胞(PBMC)源性树突状细胞(DCs)的基因表达和其功能变化的影响,进一步探讨黄芪多糖的抗AS的作用机制。方法以健康人外周血分离PBMC源性DCs和血清作为研究对象,培育5 d后,随机分为APS组和对照组。其中APS组给予200 mg/L APS孵育过夜,对照组不给干预。通过基因芯片和RT-PCR技术,观察APS处理PBMC源性DCs的免疫功能和其他基因表达的差异与AS发生发展的关系。结果与对照组相比,APS组CD36(0.97±0.23 vs5.45±1.14)、IL-27(1.08±0.22 vs 2.97±0.61)基因表达相对量显著性上调;APS组IFI16(0.98±0.18 vs 0.46±0.11)基因表达相对量显著性下调。结论适量的APS可以上调DCs膜表面与抗原递呈相关的CD36、IL-27的表达,下调IFI16的表达,对增加DCs的免疫活性,促进DCs的成熟与分化有显著的影响。APS对AS的发生发展具有明显的积极地干预作用,有着重要的积极地临床意义。展开更多
EB病毒(Epstein-Barr virus,EBV)在人群中普遍易感,其感染可累及血液、呼吸、泌尿、消化、神经等全身多个系统,亦在相关肿瘤、自身免疫病等疾病发展中扮演重要角色,严重威胁人类健康。作为一种DNA病毒,EBV可被固有免疫应答中的DNA识别...EB病毒(Epstein-Barr virus,EBV)在人群中普遍易感,其感染可累及血液、呼吸、泌尿、消化、神经等全身多个系统,亦在相关肿瘤、自身免疫病等疾病发展中扮演重要角色,严重威胁人类健康。作为一种DNA病毒,EBV可被固有免疫应答中的DNA识别受体感知,触发下游一系列免疫应答。DNA识别通路由DNA感受器、接头分子及下游效应信号组成。双链DNA感受器主要包括黑色素瘤缺乏因子2样受体(absent in melanoma 2-like receptors,ALRs)、环状GMP-AMP合酶(cyclic GMP-AMP synthase,cGAS)等;接头分子主要是干扰素基因刺激因子(stimulator of interferon genes,STING)和含有caspase招募结构域的凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a caspase recruitment domain,ASC);下游免疫效应主要包括Ⅰ型IFN、炎性小体及促炎细胞因子等。作为一种疱疹病毒科的双链DNA病毒,EBV可触发宿主复杂的固有免疫和适应性免疫应答,尤其是多种DNA识别受体介导的通路,在宿主免疫防御及病原体免疫逃避等方面均发挥关键作用。本文以DNA感受器为线索,全面总结近年来DNA识别信号在EBV感染中的活化作用、调控机制及临床相关性,以进一步理解EBV感染后宿主的固有免疫应答,为EBV感染引起的相关疾病的防治提供免疫学依据。展开更多
基金supported partly by NIH Research Grants R01AR062207,R01AR061484,and R56AI100901,Disease Targeted Research Grants from the American College of Rheumatology Research and Education Foundation.
文摘p204 is a member of the interferon-inducible p200 family proteins in mice.The p200 family has been reported to be multifunctional regulators of cell proliferation,differentiation,apoptosis and senescence.Interferon-inducible protein 16(IFI16)is regarded as the human ortholog of p204 in several studies.This is possibly due to the similarity of their structures.However the consistency of their functions is still elusive.Currently,an emerging focus has been placed upon the role of the p200 proteins as sensors for microbial DNA in innate immune responses and provides new insights into infections as well as autoimmune diseases.This review specially focuses on IFI16 and p204,the member of p200 family in human and murine respectively,and their pathophysiological roles in innate immune responses,cell differentiation and proliferation.
基金supported by the National Natural Science Foundation of China(grant no.31570875,31330019,31200559,and 81590761)the Ministry of Science and Technology of China(grant no.2014CB910400 and 2013CB911103)+2 种基金the National Science and Technology Major Project of China(grant no.2013ZX10004-602)the Beijing Nova Program(grant no.Z141102001814020)Youth Innovation Promotion Association CAS,and the special project of Ebola virus research from the president foundation of Chinese Academy of Sciences.
文摘Interferon gamma-inducible protein 16(IFI16)senses DNA in the cytoplasm and the nucleus by using two tandem hematopoietic interferon-inducible nuclear(HIN)domains,HINa and HINb,through the cooperative assembly of IFI16 filaments on double-stranded DNA(dsDNA).The role of HINa in sensing DNA is not clearly understood.Here,we describe the crystal structure of the HINa domain in complex with DNA at 2.55A°resolution and provide the first insight into the mode of DNA binding by the HINa domain.The structure reveals the presence of two oligosaccharide/nucleotide-binding(OB)folds with a unique DNA-binding surface.HINa uses loop L45 of the canonical OB2 fold to bind to the DNA backbone.The dsDNA is recognized as two single strands of DNA.Interestingly,deletion of HINb compromises the ability of IFI16 to induce IFN-b,while HINa mutants impaired in DNAbinding enhance the production of IFN-b.These results shed light on the roles of IFI16 HIN domains in DNA recognition and innate immune responses.
文摘目的研究干扰素诱导蛋白16(interferon inducible protein 16,IFI16)在银屑病中的表达及分布,探讨其在银屑病发病中的作用。方法采用RT-PCR、免疫组化的方法分别检测10例银屑病患者皮损和10例健康人皮肤组织真皮与表皮中IFI16的表达情况;采用RT-PCR、Western印记方法检测IFN-γ,TNF-α,IL-17刺激前后Ha Ca T细胞中IFI16的表达情况。结果银屑病患者皮损处IFI16的表达明显高于健康人皮肤,并且以表皮表达为主,免疫组化结果显示IFI16主要定位于银屑病患者的角质形成细胞中。银屑病相关细胞因子IFN-γ,TNF-α和IL-17可以上调角质形成细胞中IFI16的表达水平。结论IFI16在银屑病患者皮损处表达明显高于正常人皮肤,并且IFN-γ,TNF-α和IL-17可以诱导其表达上调,可能是银屑病角质形成细胞的活化机制之一。
文摘目的研究黄芪多糖(APS)对人外周血单核细胞(PBMC)源性树突状细胞(DCs)的基因表达和其功能变化的影响,进一步探讨黄芪多糖的抗AS的作用机制。方法以健康人外周血分离PBMC源性DCs和血清作为研究对象,培育5 d后,随机分为APS组和对照组。其中APS组给予200 mg/L APS孵育过夜,对照组不给干预。通过基因芯片和RT-PCR技术,观察APS处理PBMC源性DCs的免疫功能和其他基因表达的差异与AS发生发展的关系。结果与对照组相比,APS组CD36(0.97±0.23 vs5.45±1.14)、IL-27(1.08±0.22 vs 2.97±0.61)基因表达相对量显著性上调;APS组IFI16(0.98±0.18 vs 0.46±0.11)基因表达相对量显著性下调。结论适量的APS可以上调DCs膜表面与抗原递呈相关的CD36、IL-27的表达,下调IFI16的表达,对增加DCs的免疫活性,促进DCs的成熟与分化有显著的影响。APS对AS的发生发展具有明显的积极地干预作用,有着重要的积极地临床意义。
文摘EB病毒(Epstein-Barr virus,EBV)在人群中普遍易感,其感染可累及血液、呼吸、泌尿、消化、神经等全身多个系统,亦在相关肿瘤、自身免疫病等疾病发展中扮演重要角色,严重威胁人类健康。作为一种DNA病毒,EBV可被固有免疫应答中的DNA识别受体感知,触发下游一系列免疫应答。DNA识别通路由DNA感受器、接头分子及下游效应信号组成。双链DNA感受器主要包括黑色素瘤缺乏因子2样受体(absent in melanoma 2-like receptors,ALRs)、环状GMP-AMP合酶(cyclic GMP-AMP synthase,cGAS)等;接头分子主要是干扰素基因刺激因子(stimulator of interferon genes,STING)和含有caspase招募结构域的凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a caspase recruitment domain,ASC);下游免疫效应主要包括Ⅰ型IFN、炎性小体及促炎细胞因子等。作为一种疱疹病毒科的双链DNA病毒,EBV可触发宿主复杂的固有免疫和适应性免疫应答,尤其是多种DNA识别受体介导的通路,在宿主免疫防御及病原体免疫逃避等方面均发挥关键作用。本文以DNA感受器为线索,全面总结近年来DNA识别信号在EBV感染中的活化作用、调控机制及临床相关性,以进一步理解EBV感染后宿主的固有免疫应答,为EBV感染引起的相关疾病的防治提供免疫学依据。
