Upon antigen stimulation, naive T helper cells differentiate into distinct lineages to attain specialized properties and effector functions. TH17 cells, a recently identified lineage of CD4＋ effector T cells, play a ...Upon antigen stimulation, naive T helper cells differentiate into distinct lineages to attain specialized properties and effector functions. TH17 cells, a recently identified lineage of CD4＋ effector T cells, play a key role in the immune defense against fungi and extracellular bacteria, but also contribute to the pathogenesis of many autoimmune conditions. The differentiation of TH 17 cells is orchestrated by an intricate network of signaling pathways and transcriptional regulators in T cells. While the involvement of T cell-intrinsic pathways has been described extensively, we are just beginning to appreciate how TH17 cell development is shaped by extrinsic pathways, espec- ially the innate immune signals. Dendritic cells （DCs）, the most important cell type to bridge innate and adaptive immunity, drive TH17 cell differentiation by providing antigenic, costimulatory and cytokine signals. This is mediated by the recognition of innate and inflam- matory signals by DCs via pattern recognition receptors, cytokine receptors and other immunomodulatory receptors that in turn activate the intracellular signaling network. In particular, p38a MAP kinase has emerged as a critical pathway to program DC-dependent TH17 cell differentiation by integrating multiple instructive signals in DCs. Here, we summarize the current knowledge on the mechanisms by which DC-derived innate immune signals drive TH17 cell differentiation.展开更多
Objective: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge.,(Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis(AP)using a network pharmac...Objective: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge.,(Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis(AP)using a network pharmacology approach and validate the findings in animal experiments. Methods: Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics simulation.Finally, the results of network pharmacology enrichment analysis were verified by immunohistochemistry,Western blot analysis and real-time quantitative PCR, respectively. Results: Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3(MAPK3), Janus kinase 2(JAK2), signal transducer and activator of transcription 3(STAT3), protein c-Fos(FOS) were identified as core targets in the protein interaction(PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. Molecular dynamics simulation revealed that FOS-isotanshinone Ⅱ and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1β, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation(P<0.01). Conclusion: DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues,which would be functioned by regulating Th17 cell differentiation-related m RNA and protein expressions.展开更多
辅助性T细胞17(T help cell 17,Th17)是2005年发现的能够分泌白细胞介素17的CD4+T细胞,其与Th1、Th2、Tregs共同构成CD4+T细胞的4个亚群。该细胞的分化受多种细胞因子和信号分子精细而复杂地调控。转化生长因子-β(TGF-β)I、L-6I、L-23...辅助性T细胞17(T help cell 17,Th17)是2005年发现的能够分泌白细胞介素17的CD4+T细胞,其与Th1、Th2、Tregs共同构成CD4+T细胞的4个亚群。该细胞的分化受多种细胞因子和信号分子精细而复杂地调控。转化生长因子-β(TGF-β)I、L-6I、L-23和RORγt在Th17细胞的分化形成过程中起着积极的促进作用,而Socs3和Ets-1则抑制它的分化。论文对Th17细胞及其分化调控机制的研究进展做一简要综述。展开更多
目的·探讨葡萄糖对小鼠CD4^+T细胞分化的影响。方法·小鼠初始CD4^+T细胞在调节性T细胞(regulatory T cell,Treg)、Th1、Th17和Th2分化条件下,经不同浓度的葡萄糖处理5 d后,利用流式细胞术检测细胞分化的比例,实时荧光定量PCR...目的·探讨葡萄糖对小鼠CD4^+T细胞分化的影响。方法·小鼠初始CD4^+T细胞在调节性T细胞(regulatory T cell,Treg)、Th1、Th17和Th2分化条件下,经不同浓度的葡萄糖处理5 d后,利用流式细胞术检测细胞分化的比例,实时荧光定量PCR检测相关细胞因子和转录因子的基因表达水平。结果·与无糖组相比,在Treg和Th2分化的条件下,随着葡萄糖浓度升高,Treg和Th2比例增高,其关键转录因子Foxp3(forkhead box P3)、Gata3(GATA binding protein 3)与主要细胞因子转化生长因子-β、白介素-4(interleukin-4,IL-4)和IL-13的基因水平增加;而随着葡萄糖浓度升高,Th1和Th17细胞比例则降低,其相关转录因子Tbx21(T-box transcription factor 21)和RORC(RAR related orphan receptor C),以及细胞因子干扰素-γ、IL-17A、IL-17F、IL-22和细胞因子受体IL-23R的基因表达下降。结论·葡萄糖能促进Treg和Th2体外分化,而抑制Th1与Th17分化。展开更多
Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Meth...Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Methods The relevant target genes(hereinafter,“targets”)of pneumonia and colitis were separately queried on the GeneCards database.The main targets of the two diseases were then screened out according to their correlation scores and intersected to obtain those common to the two diseases.Metascape was used to analyze the main and common targets identified,and the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to enrich and analyze the common targets.Cytoscape 3.7.2 software was used to build the network diagram.Results In total,54 targets,such as TNF,IL-10,IL-6,IL-2,IL-4,TLR4,TLR2,CXCL8,IL-17A and IFNG,etc.,are common to pneumonia and colitis,which are mainly enriched in these processes such as cytokine–cytokine receptor interaction,the Tcell receptor signaling pathway,the Toll-like receptor signaling pathway and the Jak-STAT signaling pathway.The Metascape modular analysis identified 11 modules for pneumonia,six modules for colitis,and two modules for the common targets.Conclusions Pneumonia and colitis have the same pathogenic targets and mechanisms of action and finally interact with each other through inflammatory reactions and immune responses.This provides a probable molecular mechanism that explains the theory that the lung and large intestine are exteriorly and interiorly related.展开更多
文摘Upon antigen stimulation, naive T helper cells differentiate into distinct lineages to attain specialized properties and effector functions. TH17 cells, a recently identified lineage of CD4＋ effector T cells, play a key role in the immune defense against fungi and extracellular bacteria, but also contribute to the pathogenesis of many autoimmune conditions. The differentiation of TH 17 cells is orchestrated by an intricate network of signaling pathways and transcriptional regulators in T cells. While the involvement of T cell-intrinsic pathways has been described extensively, we are just beginning to appreciate how TH17 cell development is shaped by extrinsic pathways, espec- ially the innate immune signals. Dendritic cells （DCs）, the most important cell type to bridge innate and adaptive immunity, drive TH17 cell differentiation by providing antigenic, costimulatory and cytokine signals. This is mediated by the recognition of innate and inflam- matory signals by DCs via pattern recognition receptors, cytokine receptors and other immunomodulatory receptors that in turn activate the intracellular signaling network. In particular, p38a MAP kinase has emerged as a critical pathway to program DC-dependent TH17 cell differentiation by integrating multiple instructive signals in DCs. Here, we summarize the current knowledge on the mechanisms by which DC-derived innate immune signals drive TH17 cell differentiation.
基金Supported by National Natural Science Foundation of China (No.82160890, 82260899)Innovation Project of Guangxi Graduate Education (No.YCSW2023383)。
文摘Objective: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge.,(Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis(AP)using a network pharmacology approach and validate the findings in animal experiments. Methods: Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics simulation.Finally, the results of network pharmacology enrichment analysis were verified by immunohistochemistry,Western blot analysis and real-time quantitative PCR, respectively. Results: Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3(MAPK3), Janus kinase 2(JAK2), signal transducer and activator of transcription 3(STAT3), protein c-Fos(FOS) were identified as core targets in the protein interaction(PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. Molecular dynamics simulation revealed that FOS-isotanshinone Ⅱ and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1β, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation(P<0.01). Conclusion: DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues,which would be functioned by regulating Th17 cell differentiation-related m RNA and protein expressions.
文摘辅助性T细胞17(T help cell 17,Th17)是2005年发现的能够分泌白细胞介素17的CD4+T细胞,其与Th1、Th2、Tregs共同构成CD4+T细胞的4个亚群。该细胞的分化受多种细胞因子和信号分子精细而复杂地调控。转化生长因子-β(TGF-β)I、L-6I、L-23和RORγt在Th17细胞的分化形成过程中起着积极的促进作用,而Socs3和Ets-1则抑制它的分化。论文对Th17细胞及其分化调控机制的研究进展做一简要综述。
基金funding support from the Guangdong Provincial Key Construction Unit Project of Traditional Chinese Medicine Pediatrics (Guangdong Traditional Chinese Medicine Office Letter [2018] No. 202)。
文摘Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Methods The relevant target genes(hereinafter,“targets”)of pneumonia and colitis were separately queried on the GeneCards database.The main targets of the two diseases were then screened out according to their correlation scores and intersected to obtain those common to the two diseases.Metascape was used to analyze the main and common targets identified,and the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to enrich and analyze the common targets.Cytoscape 3.7.2 software was used to build the network diagram.Results In total,54 targets,such as TNF,IL-10,IL-6,IL-2,IL-4,TLR4,TLR2,CXCL8,IL-17A and IFNG,etc.,are common to pneumonia and colitis,which are mainly enriched in these processes such as cytokine–cytokine receptor interaction,the Tcell receptor signaling pathway,the Toll-like receptor signaling pathway and the Jak-STAT signaling pathway.The Metascape modular analysis identified 11 modules for pneumonia,six modules for colitis,and two modules for the common targets.Conclusions Pneumonia and colitis have the same pathogenic targets and mechanisms of action and finally interact with each other through inflammatory reactions and immune responses.This provides a probable molecular mechanism that explains the theory that the lung and large intestine are exteriorly and interiorly related.
