目的探索白细胞分化抗原6(cluster of differentiation 6,CD6)表达与子宫颈癌临床病理特征和预后的相关性,预测CD6影响肿瘤发生和发展的可能机制。方法下载TCGA-CESC数据集,使用R软件survminer包寻找截点,将资料按CD6表达量分为高表达...目的探索白细胞分化抗原6(cluster of differentiation 6,CD6)表达与子宫颈癌临床病理特征和预后的相关性,预测CD6影响肿瘤发生和发展的可能机制。方法下载TCGA-CESC数据集,使用R软件survminer包寻找截点,将资料按CD6表达量分为高表达组和低表达组。利用χ2检验比较两组各个临床病理特征的分布差异,生存分析采用Log-rank(Mantel-Cox)法。同时利用GSE44001数据集对生存分析结果进行验证。利用基因富集的方法探索CD6发挥作用的可能通路。结果子宫颈癌组织的CD6表达水平在肿瘤分期和组织学类型方面比较,差异均具有统计学意义(均P<0.05)。CD6低表达组5年总生存率和5年无瘤生存率均低于高表达组(均P<0.05)。基因富集的结果显示,CD6高表达组富集与调节免疫和细胞增殖分化相关的基因集。结论CD6低表达与子宫颈癌不良预后相关,可能作为判断子宫颈癌预后的分子及治疗的靶标。展开更多
Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors.Available evidence supports CD6,a lymphocyte surface receptor mostly expressed by T cells,as ...Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors.Available evidence supports CD6,a lymphocyte surface receptor mostly expressed by T cells,as a putative target in autoimmunity.Accordingly,a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders,including psoriasis.Here,we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology.First,an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice,as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines,namely,interleukin-17A.Thus,isolated CD4+CD62L+T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization.Second,a statistically significant association between CD6 single-nucleotide polymorphisms(rs17824933,rs11230563 and rs12360861)and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona.Taken together,these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.展开更多
The scavenger-like lymphocyte receptor CD6 is a regulator of T cell functions,and is associated with autoimmune diseases.However,the specific contribution of CD6 to autoimmunity remains unknown.Under physiological con...The scavenger-like lymphocyte receptor CD6 is a regulator of T cell functions,and is associated with autoimmune diseases.However,the specific contribution of CD6 to autoimmunity remains unknown.Under physiological conditions,CD6 associates with the T cell antigen receptor(TCR)/CD3 complex at the center of the immunological synapse and regulates T cell responses through activation-dependent recruitment of the positive regulator SLP-76 and other downstream signaling effectors.1,2 In recent years,immune-activating and immune-inhibiting functions of CD6 have been reported,indicating a dual role of CD6 in T cell activation.1 It has been postulated that the strength of TCR activation determines whether CD6 enhances or inhibits TCR signaling.1 This possible counter-regulatory role of CD6 may contribute to the control of T cell responses.展开更多
[目的]研究山茱萸新苷对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)大鼠中枢神经系统单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)表达及CD68阳性细胞浸润的影响。[方法]制备豚鼠全...[目的]研究山茱萸新苷对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)大鼠中枢神经系统单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)表达及CD68阳性细胞浸润的影响。[方法]制备豚鼠全脊髓匀浆免疫抗原,皮下注射至Lewis大鼠,建立EAE模型。设正常对照组、EAE组、山茱萸新苷组、波尼松组,每天神经功能评分,待症状达到高峰处死实验动物,用RT-PCR、Western Blot法比较各组实验动物中枢神经系统MCP-1 m RNA及蛋白的表达,免疫组织化学染色法比较各组实验动物中枢神经系统CD68阳性细胞浸润情况。[结果]正常对照组、EAE组、山茱萸新苷组、波尼松组大鼠MCP-1 m RNA的相对表达量分别为(11.265±2.928)、(401.373±55.398)、(124.987±20.244)、(75.465±7.766),MCP-1蛋白相对表达量分别为(7.458±2.570)、(24.155±1.420)、(19.568±0.863)、(17.458±1.630),CD68阳性指数分别为0%、(41.93±12.25)%、(16.08±8.70)%、(5.38±2.88)%。使用单因素方差分析法,MCP-1 m RNA的相对表达量、MCP-1蛋白相对表达量、CD68阳性指数组间差异显著,均有统计学意义(F=199.734、66.081、35.565,均P=0.000)。山茱萸新苷组与EAE组在神经功能评分、MCP-1 m RNA的相对表达量、MCP-1蛋白相对表达量、CD68阳性指数表达差异均有统计学意义(P=0.002、0.000、0.003、0.013)。[结论]山茱萸新苷可改善EAE大鼠神经功能,抑制EAE大鼠中枢神经系统MCP-1表达及CD68阳性细胞浸润。展开更多
文摘目的探索白细胞分化抗原6(cluster of differentiation 6,CD6)表达与子宫颈癌临床病理特征和预后的相关性,预测CD6影响肿瘤发生和发展的可能机制。方法下载TCGA-CESC数据集,使用R软件survminer包寻找截点,将资料按CD6表达量分为高表达组和低表达组。利用χ2检验比较两组各个临床病理特征的分布差异,生存分析采用Log-rank(Mantel-Cox)法。同时利用GSE44001数据集对生存分析结果进行验证。利用基因富集的方法探索CD6发挥作用的可能通路。结果子宫颈癌组织的CD6表达水平在肿瘤分期和组织学类型方面比较,差异均具有统计学意义(均P<0.05)。CD6低表达组5年总生存率和5年无瘤生存率均低于高表达组(均P<0.05)。基因富集的结果显示,CD6高表达组富集与调节免疫和细胞增殖分化相关的基因集。结论CD6低表达与子宫颈癌不良预后相关,可能作为判断子宫颈癌预后的分子及治疗的靶标。
基金supported by grants from the Spanish Ministerio de Economía y Competitividad(Plan Nacional I+D+i,SAF2013-46151-R and SAF2016-80535-R to FL),co-financed by the European Development Regional Fund‘A way to achieve Europe’ERDFsupported by the Sara Borrell fellowship CD15/00016 from Instituto de Salud Carlos Ⅲ.
文摘Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors.Available evidence supports CD6,a lymphocyte surface receptor mostly expressed by T cells,as a putative target in autoimmunity.Accordingly,a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders,including psoriasis.Here,we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology.First,an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice,as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines,namely,interleukin-17A.Thus,isolated CD4+CD62L+T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization.Second,a statistically significant association between CD6 single-nucleotide polymorphisms(rs17824933,rs11230563 and rs12360861)and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona.Taken together,these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.
文摘The scavenger-like lymphocyte receptor CD6 is a regulator of T cell functions,and is associated with autoimmune diseases.However,the specific contribution of CD6 to autoimmunity remains unknown.Under physiological conditions,CD6 associates with the T cell antigen receptor(TCR)/CD3 complex at the center of the immunological synapse and regulates T cell responses through activation-dependent recruitment of the positive regulator SLP-76 and other downstream signaling effectors.1,2 In recent years,immune-activating and immune-inhibiting functions of CD6 have been reported,indicating a dual role of CD6 in T cell activation.1 It has been postulated that the strength of TCR activation determines whether CD6 enhances or inhibits TCR signaling.1 This possible counter-regulatory role of CD6 may contribute to the control of T cell responses.
文摘[目的]研究山茱萸新苷对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)大鼠中枢神经系统单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)表达及CD68阳性细胞浸润的影响。[方法]制备豚鼠全脊髓匀浆免疫抗原,皮下注射至Lewis大鼠,建立EAE模型。设正常对照组、EAE组、山茱萸新苷组、波尼松组,每天神经功能评分,待症状达到高峰处死实验动物,用RT-PCR、Western Blot法比较各组实验动物中枢神经系统MCP-1 m RNA及蛋白的表达,免疫组织化学染色法比较各组实验动物中枢神经系统CD68阳性细胞浸润情况。[结果]正常对照组、EAE组、山茱萸新苷组、波尼松组大鼠MCP-1 m RNA的相对表达量分别为(11.265±2.928)、(401.373±55.398)、(124.987±20.244)、(75.465±7.766),MCP-1蛋白相对表达量分别为(7.458±2.570)、(24.155±1.420)、(19.568±0.863)、(17.458±1.630),CD68阳性指数分别为0%、(41.93±12.25)%、(16.08±8.70)%、(5.38±2.88)%。使用单因素方差分析法,MCP-1 m RNA的相对表达量、MCP-1蛋白相对表达量、CD68阳性指数组间差异显著,均有统计学意义(F=199.734、66.081、35.565,均P=0.000)。山茱萸新苷组与EAE组在神经功能评分、MCP-1 m RNA的相对表达量、MCP-1蛋白相对表达量、CD68阳性指数表达差异均有统计学意义(P=0.002、0.000、0.003、0.013)。[结论]山茱萸新苷可改善EAE大鼠神经功能,抑制EAE大鼠中枢神经系统MCP-1表达及CD68阳性细胞浸润。
