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Eomesodermin spatiotemporally orchestrates the early and late stages of NK cell development by targeting KLF2 and T-bet,respectively 认领 引用 被引量：1
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作者 Junming He Donglin Chen +4 位作者 Wei Xiong Xinlei Hou Yuhe Quan Meixiang Yang Zhongjun Dong 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2024年第7期662-673,共12页
Eomesodermin(Eomes)is a critical factor in the development of natural killer(NK)cells,but its precise role in temporal and spatial coordination during this process remains unclear.Our study revealed that Eomes plays d... Eomesodermin(Eomes)is a critical factor in the development of natural killer(NK)cells,but its precise role in temporal and spatial coordination during this process remains unclear.Our study revealed that Eomes plays distinct roles during the early and late stages of NK cell development.Specifically,the early deletion of Eomes via the CD122-Cre transgene resulted in significant blockade at the progenitor stage due to the downregulation of KLF2,another important transcription factor.ChIP-seq revealed direct binding of Eomes to the conserved noncoding sequence(CNS)of Klf2.Utilizing the CHimeric IMmune Editing(CHIME)technique,we found that deletion of the CNS region of Klf2 via CRISPRi led to a reduction in the NK cell population and developmental arrest.Moreover,constitutive activation of this specific CNS region through CRISPRa significantly reversed the severe defects in NK cell development caused by Eomes deficiency.Conversely,Ncr1-Cre-mediated terminal deletion of Eomes expedited the transition of NK cell subsets from the CD27+CD11b+phenotype to the CD27−CD11b+phenotype.Late-stage deficiency of Eomes led to a significant increase in T-bet expression,which subsequently increased the expression of the transcription factor Zeb2.Genetic deletion of one allele of Tbx21,encoding T-bet,effectively reversed the aberrant differentiation of Eomes-deficient NK cells.In summary,we utilized two innovative genetic models to elucidate the intricate mechanisms underlying Eomes-mediated NK cell commitment and differentiation. 展开更多
关键词 Natural killer cells Eomesodermin Development KLF2 T-bet
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Maternal Eomesodermin regulates zygotic nodal gene expression for mesendoderm induction in zebrafish embryos 认领 引用 被引量：6
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作者 Pengfei Xu Gaoyang Zhu +4 位作者 Yixia Wang Jiawei Sun Xingfeng Liu Ye-Guang Chen Anming Meng 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2014年第4期272-285,共14页
Development of animal embryos before zygotic genome activation at the mid blastula transition(MBT)is essentially supported by eggderived maternal products.Nodal proteins are crucial signals for mesoderm and endoderm i... Development of animal embryos before zygotic genome activation at the mid blastula transition(MBT)is essentially supported by eggderived maternal products.Nodal proteins are crucial signals for mesoderm and endoderm induction after the MBT.It remains unclear which maternal factors activate zygotic expression of nodal genes in the ventrotateral blastodermal margin of the zebrafish blastulas.In this study,we show that loss of maternal Eomesodermin a(Eomesa),a T-box transcription factor,impairs zygotic expression of the nodal genes ndr1 and ndr2 as well as mesodermal and endodermal markers,indicating an involvement in mesendoderm induction.Maternal Eomesa is also required for timely zygotic expression of the transcription factor gene mxtx2,a regulator of nodal gene expression.Eomesa directly binds to the Eomes-binding sites in the promoter or enhancer of ndr1,ndr2,and rnxtx2 to activate their transcrip-tion.Furthermore,human and mouse Nodal genes are also regulated by Eomes.Transfection of zebrafish eomesa into murine embryonic stem cells promotes mesendodermal differentiation with constant higher levels of endogenous Nodal expression,suggesting a conserved function of Eomes.Taken together,our findings reveal a conserved rote of maternal T-box transcription factors in regulating nodal gene expression and mesendoderm induction in vertebrate embryos. 展开更多
关键词 Eomesodermin Nodal transcription mesoderm endoderm embryo zebrafish
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PD-1+and TIM-3+T cells widely express commonγ-chain cytokine receptors in multiple myeloma patients,and IL-2,IL-7,IL-15 stimulation up-regulates PD-1 and TIM-3 on T cells 认领 引用 被引量：1
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作者 EGOR V.BATOROV ALISA D.INESHINA +6 位作者 TATIANA A.ARISTOVA VERA V.DENISOVA SVETLANA A.SIZIKOVA DARIA S.BATOROVA GALINA Y.USHAKOVA EKATERINA Y.SHEVELA ELENA R.CHERNYKH 《Oncology Research》 SCIE 2024年第10期1575-1587,共13页
Background:Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma(MM)progression.Simultaneously,previous studies showed the possibility of PD-1 and TIM-3 expression on T cells upo... Background:Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma(MM)progression.Simultaneously,previous studies showed the possibility of PD-1 and TIM-3 expression on T cells upon stimulation with commonγ-chain family cytokines in vitro and during homeostatic proliferation.The aim of the present work was to study the impact of homeostatic proliferation on the expansion of certain T cell subsets upregulating PD-1 and TIM-3 checkpoint molecules.Methods:The expression of CD25,CD122,CD127 commonγ-chain cytokine receptors,phosphorylated signal transducer and activator of transcription-5(pSTAT5)and eomesodermin(EOMES)was comparatively assessed with flow cytometry in PD-1-and TIM-3-negative and positive T cells before the conditioning and during the first post-transplant month in peripheral blood samples of MM patients.Results:Substantial proportions of PD-1-and TIM-3-positive T lymphocytes expressed commonγ-chain cytokine receptors and pSTAT5.Frequencies of cytokine receptor expressing cells were significantly higher within TIM-3+T cells compared to PD-1+TIM-3−subsets.Considerable proportions of both PD-1-/TIM-3-negative and positive CD8+T cells express EOMES,while only moderate frequencies of CD4+PD-1+/TIM-3+T cells up-regulate this transcription factor.Besides,the surface presence of CD25 and intranuclear expression of EOMES in CD4+T cells were mutually exclusive regardless of PD-1 and TIM-3 expression.The stimulation with commonγ-chain cytokines up-regulates PD-1 and TIM-3 during the proliferation of initially PD-1/TIM-3-negative T cells but fails to expand initially PD-1+and TIM-3+T cell subsets in vitro.Conclusions:Both PD-1 and TIM-3 expressing T cells appear to be able to respond to homeostatic cytokine stimulation.Differences in commonγ-chain cytokine receptor expression between PD-1+and TIM-3+T cells may reflect functional dissimilarity of these cell subsets.Checkpoint blockade appears to alleviate lymphopenia-induced proliferation of PD-1+T cells but may raise the possibility of immune-mediated adverse events. 展开更多
关键词 Autologous hematopoietic stem cell transplantation(AHSCT) CD25 CD122 Eomesodermin(EOMES) Homeostatic proliferation
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斑马鱼eomes基因在黑尾近红鲌胚胎发育中的整体原位杂交分析 认领 引用
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作者 吕海英 杨启文 +2 位作者 殷海成 宋平 张训蒲 《华中农业大学学报》 CAS 北大核心 2008年第3期419-421,共3页
关键词 斑马鱼 eomesodermin 黑尾近红鲐 胚胎发育 整体原位杂交
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转录因子Eomes调控CD8+T细胞效应功能、免疫记忆和耗竭 认领 引用 被引量：1
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作者 伍诣娴 朱一蓓 《现代免疫学》 CAS 北大核心 2022年第5期416-420,共5页
脱中胚蛋白(Eomesodermin, Eomes)是与CD8+T细胞分化和效应功能密切相关的T-box家族转录因子。在应对慢性病毒感染及抗肿瘤免疫应答的过程中,Eomes可促进初始CD8+T细胞分化为效应CD8+T细胞并增强其效应功能,驱动经典记忆T细胞... 脱中胚蛋白(Eomesodermin, Eomes)是与CD8+T细胞分化和效应功能密切相关的T-box家族转录因子。在应对慢性病毒感染及抗肿瘤免疫应答的过程中,Eomes可促进初始CD8+T细胞分化为效应CD8+T细胞并增强其效应功能,驱动经典记忆T细胞的形成和维持,并且与CD8+T细胞的耗竭密切相关。文章就Eomes在调控CD8+T细胞效应功能,免疫记忆和耗竭方面的作用及潜在机制展开探讨,以发掘抗肿瘤免疫治疗的新策略。 展开更多
关键词 脱中胚蛋白 CD8+T细胞 效应功能 免疫记忆 T细胞耗竭
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