调节性T细胞(regulatory T cell, Treg)是一类具有免疫抑制功能的T细胞亚群。表达于Treg细胞表面的CD39和CD73可将细胞外的三磷酸腺苷(ATP)依次分解为腺苷,进而调节靶细胞的功能,发挥免疫抑制功能。大量研究显示Treg细胞在过敏性疾病中...调节性T细胞(regulatory T cell, Treg)是一类具有免疫抑制功能的T细胞亚群。表达于Treg细胞表面的CD39和CD73可将细胞外的三磷酸腺苷(ATP)依次分解为腺苷,进而调节靶细胞的功能,发挥免疫抑制功能。大量研究显示Treg细胞在过敏性疾病中发挥重要作用,本文对Treg 细胞CD39-CD73-腺苷通路在过敏性疾病中的作用机制进行综述,为疾病治疗探究潜在的靶点。展开更多
目的 分析肺癌合并脓毒症患者中外周单核细胞HLA-DR、外周血CD39^(+)Tregs水平和IL-10表达水平对病情及预后评估的价值。方法 选择2020年9月至2021年12月我院收治的肺癌合并脓毒症的患者68例,根据其严重程度分为脓毒症组38例,脓毒性休克...目的 分析肺癌合并脓毒症患者中外周单核细胞HLA-DR、外周血CD39^(+)Tregs水平和IL-10表达水平对病情及预后评估的价值。方法 选择2020年9月至2021年12月我院收治的肺癌合并脓毒症的患者68例,根据其严重程度分为脓毒症组38例,脓毒性休克组30例;同期36例未合并脓毒症的肺癌患者为对照组;测定各组患者入院后外周单核细胞HLA-DR、外周血CD39^(+)Treg及IL-10的水平,分析三种指标与严重程度的相关性,采用ROC曲线分析三种指标及联合检测对脓毒症严重程度和预后评估的能力。结果 (1)脓毒症组血清中的CD39^(+)Treg比例、IL-10水平均显著高于对照组(3.92±1.35 vs. 2.14±0.86%)、(37.08±5.32 vs. 9.22±1.75)pg/ml(P<0.01),mHLA-DR水平在感染前7 d均低于脓毒性休克组和对照组,P<0.01;在入院第7天脓毒症组中HLA-DR降至最低,与入院时水平差异有显著性(91.07±1.14 vs. 84.59±0.7%,P<0.01);(2)68例脓毒症肺癌患者中,死亡22例;与生存者相比,死亡者ΔHLA-DR7水平明显降低,CD39^(+)Treg比例、IL-10水平明显升高,P<0.01;(3)脓毒症组中多因素Logistic回归分析显示ΔHLA-DR7(OR=2.195,P<0.001)、CD39^(+)Treg(OR=2.853,P=0.015)、IL-10(OR=1.868,P=0.002)与APACHEⅡ及SOFA评分是脓毒症预后不良的危险因素;(4)ΔHLA-DR7评价脓毒症预后的曲线下面积为0.911,截断值为8.7%时,敏感度为89.28%,特异度为97.6%,大于CD39^(+)Treg和IL-10,P<0.01;三种指标联合的预后评估能力(曲线下面积为0.925,敏感度为96.61%,特异度为94.32%)明显高于三者的单一检测或两两联合检测。结论 ΔHLA-DR7是肺癌伴脓毒症严重程度和预后评估的一个良好指标,ΔHLA-DR7与CD39^(+)Treg和IL-10三者联合能够显著提高脓毒症的诊断和预后评估的水平。展开更多
Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,s...Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,such as rheumatoid arthritis(RA).As multipotent progenitor cells,mesenchymal stem cells(MSCs),can regulate dendritic cells(DCs)to restore their immunosuppressive function and prevent disease development.However,the underlying mechanisms of MSCs in regulating DCs still need to be better defined.Simultaneously,the delivery system for MSCs also influences their function.Herein,MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ,maximizing efficacy in vivo.The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines.In the collagen-induced arthritis(CIA)mice model,alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39^(+)CD73^(+)on MSCs.These enzymes hydrolyze ATP to adenosine and activate A_(2A/2B)receptors on immature DCs,further promoting the phenotypic transformation of DCs to tol DCs and regulating naive T cells to Tregs.Therefore,encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression.This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.展开更多
文摘调节性T细胞(regulatory T cell, Treg)是一类具有免疫抑制功能的T细胞亚群。表达于Treg细胞表面的CD39和CD73可将细胞外的三磷酸腺苷(ATP)依次分解为腺苷,进而调节靶细胞的功能,发挥免疫抑制功能。大量研究显示Treg细胞在过敏性疾病中发挥重要作用,本文对Treg 细胞CD39-CD73-腺苷通路在过敏性疾病中的作用机制进行综述,为疾病治疗探究潜在的靶点。
文摘目的 分析肺癌合并脓毒症患者中外周单核细胞HLA-DR、外周血CD39^(+)Tregs水平和IL-10表达水平对病情及预后评估的价值。方法 选择2020年9月至2021年12月我院收治的肺癌合并脓毒症的患者68例,根据其严重程度分为脓毒症组38例,脓毒性休克组30例;同期36例未合并脓毒症的肺癌患者为对照组;测定各组患者入院后外周单核细胞HLA-DR、外周血CD39^(+)Treg及IL-10的水平,分析三种指标与严重程度的相关性,采用ROC曲线分析三种指标及联合检测对脓毒症严重程度和预后评估的能力。结果 (1)脓毒症组血清中的CD39^(+)Treg比例、IL-10水平均显著高于对照组(3.92±1.35 vs. 2.14±0.86%)、(37.08±5.32 vs. 9.22±1.75)pg/ml(P<0.01),mHLA-DR水平在感染前7 d均低于脓毒性休克组和对照组,P<0.01;在入院第7天脓毒症组中HLA-DR降至最低,与入院时水平差异有显著性(91.07±1.14 vs. 84.59±0.7%,P<0.01);(2)68例脓毒症肺癌患者中,死亡22例;与生存者相比,死亡者ΔHLA-DR7水平明显降低,CD39^(+)Treg比例、IL-10水平明显升高,P<0.01;(3)脓毒症组中多因素Logistic回归分析显示ΔHLA-DR7(OR=2.195,P<0.001)、CD39^(+)Treg(OR=2.853,P=0.015)、IL-10(OR=1.868,P=0.002)与APACHEⅡ及SOFA评分是脓毒症预后不良的危险因素;(4)ΔHLA-DR7评价脓毒症预后的曲线下面积为0.911,截断值为8.7%时,敏感度为89.28%,特异度为97.6%,大于CD39^(+)Treg和IL-10,P<0.01;三种指标联合的预后评估能力(曲线下面积为0.925,敏感度为96.61%,特异度为94.32%)明显高于三者的单一检测或两两联合检测。结论 ΔHLA-DR7是肺癌伴脓毒症严重程度和预后评估的一个良好指标,ΔHLA-DR7与CD39^(+)Treg和IL-10三者联合能够显著提高脓毒症的诊断和预后评估的水平。
基金supported by the National Key R&D Program of China(No.2020YFA0908004)the National Natural Science Foundation of China(Nos.82293684,82293680,82273936,82273929)+1 种基金CAMS Innovation Fund for Medical Science(No.2021-I2M-1-028,2022-I2M-2-002,2022-I2M-1-014,China)Natural Science Fund for Distinguished Young Scholars of Tianjin(No.21JCJQJC00020,China)。
文摘Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,such as rheumatoid arthritis(RA).As multipotent progenitor cells,mesenchymal stem cells(MSCs),can regulate dendritic cells(DCs)to restore their immunosuppressive function and prevent disease development.However,the underlying mechanisms of MSCs in regulating DCs still need to be better defined.Simultaneously,the delivery system for MSCs also influences their function.Herein,MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ,maximizing efficacy in vivo.The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines.In the collagen-induced arthritis(CIA)mice model,alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39^(+)CD73^(+)on MSCs.These enzymes hydrolyze ATP to adenosine and activate A_(2A/2B)receptors on immature DCs,further promoting the phenotypic transformation of DCs to tol DCs and regulating naive T cells to Tregs.Therefore,encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression.This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.
