|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Sin1/mTORC2 regulate B cell growth and metabolism by activating mTORC1 and Myc显示文摘Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely understood.In this study,Sin1,a key component of mTOR complex 2(mTORC2),specifically regulates B cell growth and metabolism.Genetic ablation of Sin1 in B cells reduces the cell size at either the transitional stage or upon antigen stimulation and severely impairs metabolism.Sin1 deficiency also severely impairs B-cell proliferation,antibody responses,and anti-viral immunity.At the molecular level,Sin1 controls the expression and stability of the c-Myc protein and maintains the activity of mTORC1 through the Akt-dependent inactivation of GSK3 and TSC1/2,respectively.Therefore,our study reveals a novel and specific role for Sin1 in coordinating the activation of mTORC2 and mTORC1 to control B cell growth and metabolism. | Man Li Adam S.Lazorchak Xinxing Ouyang Huihui Zhang Hongzhi Liu Omotooke A.Arojo Lichong Yan Jingsi Jin Yuheng Han Guojun Qu Yuhong Fu Xiaocao Xu Xiaobo Liu Wenqian Zhang Zhengfeng Yang Chuan Ruan Qijun Wang Dou Liu Chuanxin Huang Lu Lu Shibo Jiang Fubin Li Bing Su | 2019 | Cellular & Molecular Immunology2019，16，9： | 4 |
| 2 | The mechanosensitive lncRNA Neat1 promotes osteoblast function through paraspeckle-dependent Smurf1 mRNA retention显示文摘Mechanical stimulation plays an important role in bone remodeling. Exercise-induced mechanical loading enhances bone strength,whereas mechanical unloading leads to bone loss. Increasing evidence has demonstrated that long noncoding RNAs(lnc RNAs) play key roles in diverse biological, physiological and pathological contexts. However, the roles of lnc RNAs in mechanotransduction and their relationships with bone formation remain unknown. In this study, we screened mechanosensing lnc RNAs in osteoblasts and identified Neat1, the most clearly decreased lnc RNA under simulated microgravity. Of note, not only Neat1 expression but also the specific paraspeckle structure formed by Neat1 was sensitive to different mechanical stimulations, which were closely associated with osteoblast function. Paraspeckles exhibited small punctate aggregates under simulated microgravity and elongated prolate or larger irregular structures under mechanical loading. Neat1 knockout mice displayed disrupted bone formation, impaired bone structure and strength, and reduced bone mass. Neat1 deficiency in osteoblasts reduced the response of osteoblasts to mechanical stimulation. In vivo, Neat1 knockout in mice weakened the bone phenotypes in response to mechanical loading and hindlimb unloading stimulation. Mechanistically, paraspeckles promoted nuclear retention of E3 ubiquitin ligase Smurf1 m RNA and downregulation of their translation, thus inhibiting ubiquitination-mediated degradation of the osteoblast master transcription factor Runx2, a Smurf1 target. Our study revealed that Neat1 plays an essential role in osteoblast function under mechanical stimulation, which provides a paradigm for the function of the lnc RNA-assembled structure in response to mechanical stimulation and offers a therapeutic strategy for long-term spaceflight-or bedrest-induced bone loss and age-related osteoporosis. | Caizhi Liu Xingcheng Gao Yuheng Li Weijia Sun Youjia Xu Yingjun Tan Ruikai Du Guohui Zhong Dingsheng Zhao Zizhong Liu Xiaoyan Jin Yinlong Zhao Yinbo Wang Xinxin Yuan Junjie Pan Guodong Yuan Youyou Li Wenjuan Xing Guanghan Kan Yanqing Wang Qi Li Xuan Han Jianwei Li Shukuan Ling Yingxian Li | 2022 | Bone Research2022，10，2： | 3 |
| 3 | Metabolic regulation of T cell development by Sinl-mTORC2 is mediated by pyruvate kinase M2显示文摘Glucose metabolism plays a key role in thymocyte development. The mammalian target of rapamycin complex 2 (mT0RC2) is a critical regulator of cell growth and metabolism, but its role in early thymocyte development and metabolism has not been fully studied. We show here that genetic ablation of Sinl, an essential component of mTORC2, in T lineage cells results in severely impaired thymocyte development at the CD4^- CD8^- double negative (DN) stages but not at the CD4^+ CD8^+ double positive (DP) or later stages. Notably, Sinl-deficient DN thymocytes show markedly reduced proliferation and glycolysis.Importantly, we discover that the M2 isoform of pyruvate kinase (PKM2) is a novel and crucial Sinl effector in promoting DN thymocyte development and metabolism. At the molecular level, we show that Sinl-mTORC2 controls PKM2 expression through an AKT-dependent PPAR-y nuclear translocation. Together, our study unravels a novel mTORC2-PPAR-γ-PKM2 pathway in immune-metabolic regulation of early thymocyte development. | Xinxing Ouyang Yuheng Han Guojun Qu Man Li Ningbo Wu Hongzhi Liu Omotooke Arojo Hongxiang Sun Xiaobo Liu Dou Liu Lei Chen Qiang Zou Bing Su | 2019 | Journal of Molecular Cell Biology2019，11，2： | 3 |
| 4 | MAP3K2 augments Th1 cell differentiation via IL-18 to promote T cell-mediated colitis显示文摘T cell-mediated immunity in the intestine is stringently controlled to ensure proper immunity against pathogenic microbes and to prevent autoimmunity,a known cause of inflammatory bowel disease.However,precisely how T cells regulate intestine immunity remains to be fully understood.In this study,we found that mitogen-activated protein kinase kinase kinase 2(MAP3K2)is required for the CD4^(+)T cell-mediated inflammation in the intestine.Using a T cell transfer colitis model,we found that MAP3K2-deficient naïve CD4^(+)T cells had a dramatically reduced ability to induce colitis compared to wild type T cells.In addition,significantly fewer IFN-γ-but more IL-17A-producing CD4^(+)T cells in the intestines of mice receiving MAP3K2-deficient T cells than in those from mice receiving wild type T cells was observed.Interestingly,under well-defined in vitro differentiation conditions,MAP3K2-deficient naïve T cells were not impaired in their ability to differentiate into Th1,Th17 and Treg.Furthermore,the MAP3K2-regulated colitis severity was mediated by Th1 but not Th17 cells in the intestine.At the molecular level,we showed that MAP3K2-mediated Th1 cell differentiation in the intestine was regulated by IL-18 and required specific JNK activation.Together,our study reveals a novel regulatory role of MAP3K2 in intestinal T cell immunity via the IL-18-MAP3K2-JNK axis and may provide a novel target for intervention in T cell-mediated colitis. | Ningbo Wu Dongping Chen Hongxiang Sun Jianmei Tan Yao Zhang Tianyu Zhang Yuheng Han Hongzhi Liu Xinxing Ouyang Xiao-Dong Yang Xiaoyin Niu Jie Zhong Zhengting Wang Bing Su | 2021 | Science China(Life Sciences)2021，64，3： | 3 |
| 5 | Urban-rural transformation in relation to cultivated land conversion in China:Implications for optimizing land use and balanced regional development显示文摘 | Li Yuheng Li Yurui Westlund Hans | 2015 | Land Use Policy2015，47，： | 1 |
| 6 | Author Correction:Regulation of CD8^(+)T memory and exhaustion by the mTOR signals显示文摘Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/s41423-023-01064-3,published online 15 August 2023 In this article the author name Yuheng Han was incorrectly written as Yuhen Han.The original article has been corrected. | Yao Chen Ziyang Xu Hongxiang Sun Xinxing Ouyang Yuheng Han Haihui Yu Ningbo Wu Yiting Xie Bing Su | 2023 | Cellular & Molecular Immunology2023，20，11： | 0 |
| 7 | HuR-mediated nucleocytoplasmic translocation of HOTAIR relieves its inhibition of osteogenic differentiation and promotes bone formation显示文摘Bone marrow mesenchymal stem cell(BMSC)osteogenic differentiation and osteoblast function play critical roles in bone formation,which is a highly regulated process.Long noncoding RNAs(lncRNAs)perform diverse functions in a variety of biological processes,including BMSC osteogenic differentiation.Although several studies have reported that HOX transcript antisense RNA(HOTAIR)is involved in BMSC osteogenic differentiation,its effect on bone formation in vivo remains unclear.Here,by constructing transgenic mice with BMSC(Prx1-HOTAIR)-and osteoblast(Bglap-HOTAIR)-specific overexpression of HOTAIR,we found that Prx1-HOTAIR and Bglap-HOTAIR transgenic mice show different bone phenotypes in vivo.Specifically,Prx1-HOTAIR mice showed delayed bone formation,while Bglap-HOTAIR mice showed increased bone formation.HOTAIR inhibits BMSC osteogenic differentiation but promotes osteoblast function in vitro.Furthermore,we identified that HOTAIR is mainly located in the nucleus of BMSCs and in the cytoplasm of osteoblasts.HOTAIR displays a nucleocytoplasmic translocation pattern during BMSC osteogenic differentiation.We first identified that the RNA-binding protein human antigen R(HuR)is responsible for HOTAIR nucleocytoplasmic translocation.HOTAIR is essential for osteoblast function,and cytoplasmic HOTAIR binds to miR-214 and acts as a ceRNA to increase Atf4 protein levels and osteoblast function.BglapHOTAIR mice,but not Prx1-HOTAIR mice,showed alleviation of bone loss induced by unloading.This study reveals the importance of temporal and spatial regulation of HOTAIR in BMSC osteogenic differentiation and bone formation,which provides new insights into precise regulation as a target for bone loss. | Yuheng Li Weijia Sun Jianwei Li Ruikai Du Wenjuan Xing Xinxin Yuan Guohui Zhong Dingsheng Zhao Zizhong Liu Xiaoyan Jin Junjie Pan Youyou Li Qi Li Guanghan Kan Xuan Han Shukuan Ling Xiqing Sun Yingxian Li | 2023 | Bone Research2023，11，4： | 0 |
| 8 | Electron-electron interactions in monolayer graphene quantum capacitors显示文摘我们表明电子电子(e-e ) 的效果在单层 graphene 量电容器的相互作用。Ultrathin 钇氧化物在最高门的设备几何学作为绝缘的层显示出优秀性能。结构和钇氧化物层的绝缘的常数小心地被学习了。从量电容检索的反的压缩的可能性在不同温度在单层 graphene 为 e-e 相互作用与理论预言相当同意了很好。我们发现电子洞水坑在 graphene 在低密度的搬运人区域起了一个重要作用。由认为温度依赖者费用是变化,我们建立了一个模型解释在迪拉克点附近在单层 graphene 从 e-e 相互作用发源的舍入效果。 | Xiaolong Chen Lin Wang Wei Li Yang Wang Zefei Wu Mingwei Zhang Yu Han Yuheng He Ning Wang | 2013 | Nano Research2013，6，8： | 0 |
| 9 | scRNA-seq profiling of neonatal and adult thymus-derived CD4+ T cells by a T cell origin-time tracing model显示文摘It is well documented that the neonatal thymus-derived (neonatal-TD) regulatory T cells (Treg) are essential to prevent lethal autoimmune diseases and allergies, and neonatal and adult thymus possesses distinct output potentials for naïve T cells, including Treg. However, the molecular features and detailed functional differences between neonatal-TD and adult thymus-derived (adult-TD) T cells in terms of their ability to maintain immune homeostasis during long-term environmental influences are still largely unknown, partially due to the lack of appropriate animal models to precisely trace these cells at specific time points. In this study, neonatal-TD and adult-TD CD4+ T cells from the spleen and Peyer's patches were traced for 9 weeks by a T cell origin-time tracing mouse model and analysed by single-cell RNA sequencing. More Treg but fewer naïve T cells were found in neonatal-TD CD4+ T cells from both tissues than those from adult-TD counterparts. Interestingly, the neonatal-TD Treg in both the spleen and Peyer's patches exhibited augmented expression of Foxp3, Gata3, Ctla4, Icos, Il2ra, Tgfb1, and Nrp1, as well as enriched Gene Ontology terms like T cell activation and tolerance induction, indicating an enhanced immunosuppressive function. These results were further confirmed by flow cytometry analysis and in vitro immune suppression assays. Flow cytometry also revealed a significantly higher proportion of neonatal-TD Treg in total Treg than that of adult-TD counterparts, suggesting the longer lifespan of neonatal-TD Treg. To investigate the intrinsic features of neonatal-TD and adult-TD CD4+ T cells, a shortened tracing time was performed. Surprisingly, the neonatal-TD and adult-TD CD4+ T cells had similar proportions of Treg and did not exhibit significant differences in Foxp3, Gata3, Ctla4, Icos, Il2ra, and Tgfb1 expression levels after tracing for 12 days. On the other hand, neonatal-TD Treg present an increased Nrp1 expression level compared with adult-TD counterparts, indicating the enhanced stability. Together, our work reveals that the neonatal-TD Treg are more immunosuppressive, which is likely shaped primarily by environmental factors. | Yuheng Han Xinxing Ouyang Yao Chen Shujing Lai Hongxiang Sun Ningbo Wu Chun Ruan Limin Lu Bing Su | 2022 | Journal of Molecular Cell Biology2022，14，12： | 0 |
| 10 | Regulation of CD8^(+)T memory and exhaustion by the mTOR signals显示文摘CD8^(+)T cells are the key executioners of the adaptive immune arm,which mediates antitumor and antiviral immunity.Naïve CD8^(+)T cells develop in the thymus and are quickly activated in the periphery after encountering a cognate antigen,which induces these cells to proliferate and differentiate into effector cells that fight the initial infection.Simultaneously,a fraction of these cells become long-lived memory CD8^(+)T cells that combat future infections.Notably,the generation and maintenance of memory cells is profoundly affected by various in vivo conditions,such as the mode of primary activation(e.g.,acute vs.chronic immunization)or fluctuations in host metabolic,inflammatory,or aging factors.Therefore,many T cells may be lost or become exhausted and no longer functional.Complicated intracellular signaling pathways,transcription factors,epigenetic modifications,and metabolic processes are involved in this process.Therefore,understanding the cellular and molecular basis for the generation and fate of memory and exhausted CD8^(+)cells is central for harnessing cellular immunity.In this review,we focus on mammalian target of rapamycin(mTOR),particularly signaling mediated by mTOR complex(mTORC)2 in memory and exhausted CD8^(+)T cells at the molecular level. | Yao Chen Ziyang Xu Hongxiang Sun Xinxing Ouyang Yuheng Han Haihui Yu Ningbo Wu Yiting Xie Bing Su | 2023 | Cellular & Molecular Immunology2023，20，9： | 0 |
| 11 | The phosphatidylinositol(4,5)-bisphosphate-Rab35 axis regulates migrasome formation显示文摘Migrasomes are recently discovered organelles,which are formed on the ends or branch points of retraction fibers at the trailing edge of migrating cells.Previously,we showed that recruitment of integrins to the site of migrasome formation is essential for migrasome biogenesis.In this study,we found that prior to migrasome formation,PIP5K1A,a PI4P kinase which converts PI4P into PI(4,5)P_(2),is recruited to migrasome formation sites.The recruitment of PIP5K1A results in generation of PI(4,5)P_(2) at the migrasome formation site.Once accumulated,PI(4,5)P_(2) recruits Rab35 to the migrasome formation site by interacting with the C-terminal polybasic cluster of Rab35.We further demonstrated that active Rab35 promotes migrasome formation by recruiting and concentrating integrinα5 at migrasome formation sites,which is likely mediated by the interaction between integrinα5 and Rab35.Our study identifies the upstream signaling events orchestrating migrasome biogenesis. | Tianlun Ding Jinyao Ji Weiying Zhang Yuheng Liu Boqi Liu Yiyang Han Chunlai Chen Li Yu | 2023 | Cell Research2023，33，8： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员