调节性T细胞(regulatory T cell,Treg)在抑制免疫方面具有独特的作用,是宿主维持机体免疫稳态的主要细胞。近年来研究发现,Treg细胞可继续分化为多种亚型,在不同的组织环境和免疫应答中会适应性表现辅助性T细胞(helper T lymphocytes,Th...调节性T细胞(regulatory T cell,Treg)在抑制免疫方面具有独特的作用,是宿主维持机体免疫稳态的主要细胞。近年来研究发现,Treg细胞可继续分化为多种亚型,在不同的组织环境和免疫应答中会适应性表现辅助性T细胞(helper T lymphocytes,Th)的特殊表型,表达与Th相关的转录因子,发挥独特的功能特性。肌腱膜纤维肉瘤原癌基因转录因子(c-musculoaponeurotic-fibrosarcoma,c-Maf)在Treg细胞的适应性分化过程有着重要作用。本文就c-Maf在Treg细胞中的特化作用做一简要综述,其中主要涉及表达核激素受体视黄酸受体相关孤儿受体γt(receptor-related orphan receptorγt,RORγt)Treg细胞和表达B细胞淋巴瘤蛋白6(B-cell lymphoma 6,Bcl-6)的滤泡调节性T细胞(follicular regulatory T cell,Tfr)的形成,以进一步讨论Treg细胞介导的免疫机制。展开更多
MiRNAs are integral for maintaining immune homeostasis and self-tolerance.In this study,qPCR analyses were performed to determine which miRNAs play an important role in wound healing.Next,an experiment in a model of w...MiRNAs are integral for maintaining immune homeostasis and self-tolerance.In this study,qPCR analyses were performed to determine which miRNAs play an important role in wound healing.Next,an experiment in a model of wound healing was performed,and histology,mRNA expression and T-cell subpopulations in wound tissue were analyzed.The accelerated experiments were performed by local injection of either rIL-17A and/or rlL-9 after wound healing.In vitro,the differentiation of Thl7/Th9 in miR-155^+/+ or miR-155^-/- mice was investigated,and the target genes of miR155 were analyzed.From our findings,miR-155^-/- in mice promoted wound healing and weakened T cell-mediated inflammation,especially in IL-17/IL-9,and less severe skin fibrosis developed in the mice.rIL-17A and/or rIL-9 could exacerbate inflammatory injury and delay wound healing.We also demonstrated that miR-155^-/- led to a defect in the differentiation of Th17/Th9 in vitro,and this effect of IL-17/IL-9 might be related to the expression of C-maf,which is a target gene of miR155.MiR-155 regulated IL-17/IL-9-related inflammation in wound healing and might be a potential therapeutic target to attenuate the inflammatory response in wound tissue and promote the closure of wound injuries.展开更多
Glutathione(GSH),a tripeptide that is present in all mammalian tissues,is especially highly concentrated in the liver.GSH synthesis occurs via two adenosine triphosphate(ATP)-requiring enzymatic steps:the first is rat...Glutathione(GSH),a tripeptide that is present in all mammalian tissues,is especially highly concentrated in the liver.GSH synthesis occurs via two adenosine triphosphate(ATP)-requiring enzymatic steps:the first is rate-limiting,catalyzed by glutamate-cysteine ligase,generates g-glutamylcysteine from gluta-mate and cysteine;the second is catalyzed by GSH synthetase,generates GSH from g-glutamylcysteine and glycine.GSH defends against oxidative stress,participates in detoxification of xenobiotics,de-termines the redox status of the cell,and regulates vital processes such as growth and apoptosis.Hepatic GSH plays a central role in the interorgan GSH homeostasis because sinusoidal efflux of hepatic GSH determines plasma GSH level.In liver diseases GSH homeostasis is perturbed by multiple mechanisms.Hepatic GSH biosynthesis is impaired in cholestatic liver injury,endotoxemia,and fibrotic injury largely because the expression of the GSH synthetic enzymes falls.Lower hepatic GSH level further exacerbates and perpetuates ongoing liver injury.However,in hepatocellular carcinoma GSH synthetic enzymes are upregulated and this may play a role in chemoresistance.This review focuses on the current under-standing of hepatic GSH synthesis in health and disease.展开更多
文摘调节性T细胞(regulatory T cell,Treg)在抑制免疫方面具有独特的作用,是宿主维持机体免疫稳态的主要细胞。近年来研究发现,Treg细胞可继续分化为多种亚型,在不同的组织环境和免疫应答中会适应性表现辅助性T细胞(helper T lymphocytes,Th)的特殊表型,表达与Th相关的转录因子,发挥独特的功能特性。肌腱膜纤维肉瘤原癌基因转录因子(c-musculoaponeurotic-fibrosarcoma,c-Maf)在Treg细胞的适应性分化过程有着重要作用。本文就c-Maf在Treg细胞中的特化作用做一简要综述,其中主要涉及表达核激素受体视黄酸受体相关孤儿受体γt(receptor-related orphan receptorγt,RORγt)Treg细胞和表达B细胞淋巴瘤蛋白6(B-cell lymphoma 6,Bcl-6)的滤泡调节性T细胞(follicular regulatory T cell,Tfr)的形成,以进一步讨论Treg细胞介导的免疫机制。
基金the Natural Science Foundation of Hubei Province(No.2018CFC819)Health Commission of Hubei Province Scientific Research Project(No.WJ2019F163 and No.WJ2019F165).
文摘MiRNAs are integral for maintaining immune homeostasis and self-tolerance.In this study,qPCR analyses were performed to determine which miRNAs play an important role in wound healing.Next,an experiment in a model of wound healing was performed,and histology,mRNA expression and T-cell subpopulations in wound tissue were analyzed.The accelerated experiments were performed by local injection of either rIL-17A and/or rlL-9 after wound healing.In vitro,the differentiation of Thl7/Th9 in miR-155^+/+ or miR-155^-/- mice was investigated,and the target genes of miR155 were analyzed.From our findings,miR-155^-/- in mice promoted wound healing and weakened T cell-mediated inflammation,especially in IL-17/IL-9,and less severe skin fibrosis developed in the mice.rIL-17A and/or rIL-9 could exacerbate inflammatory injury and delay wound healing.We also demonstrated that miR-155^-/- led to a defect in the differentiation of Th17/Th9 in vitro,and this effect of IL-17/IL-9 might be related to the expression of C-maf,which is a target gene of miR155.MiR-155 regulated IL-17/IL-9-related inflammation in wound healing and might be a potential therapeutic target to attenuate the inflammatory response in wound tissue and promote the closure of wound injuries.
文摘Glutathione(GSH),a tripeptide that is present in all mammalian tissues,is especially highly concentrated in the liver.GSH synthesis occurs via two adenosine triphosphate(ATP)-requiring enzymatic steps:the first is rate-limiting,catalyzed by glutamate-cysteine ligase,generates g-glutamylcysteine from gluta-mate and cysteine;the second is catalyzed by GSH synthetase,generates GSH from g-glutamylcysteine and glycine.GSH defends against oxidative stress,participates in detoxification of xenobiotics,de-termines the redox status of the cell,and regulates vital processes such as growth and apoptosis.Hepatic GSH plays a central role in the interorgan GSH homeostasis because sinusoidal efflux of hepatic GSH determines plasma GSH level.In liver diseases GSH homeostasis is perturbed by multiple mechanisms.Hepatic GSH biosynthesis is impaired in cholestatic liver injury,endotoxemia,and fibrotic injury largely because the expression of the GSH synthetic enzymes falls.Lower hepatic GSH level further exacerbates and perpetuates ongoing liver injury.However,in hepatocellular carcinoma GSH synthetic enzymes are upregulated and this may play a role in chemoresistance.This review focuses on the current under-standing of hepatic GSH synthesis in health and disease.
