JOURNAL OF LEUKOCYTE BIOLOGY
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2025
·
IF 3.1
Song Zichen,Wang Jiangrong,Zheng Zhihang,He Zhixiang,Xun Jingna,Gu Ling,Shen Yinzhong,Chen Jun
Inhibiting the metabolic activity of CD4+ T cells can effectively reduce HIV infection. Mitochondria, as critical organelles in eukaryotic metabolism, play a significant role in the progression of many diseases. The change of mitochondrial dynamics is an important process of mitochondrial regulation of cell metabolic activity. However, it remains uncertain whether regulating mitochondrial dynamics is a viable approach to reducing HIV infection. In this study, we demonstrated that promoting mitochondrial fusion in Jurkat cells through treatment with the mitochondrial fusion promoter M1 and the dynamin-related protein 1 (Drp1) inhibitor Mdivi1 conferred resistance to single-round VSVG-HIVNL4-3-GFP viral infection. Targeted metabolomics analysis revealed and subsequently confirmed the potential involvement of citrate in reducing HIV infection, which has been subsequently verified. And we found that plasma citrate level was negatively associated with HIV disease progression. Multi-omics results showed that citric acid leads to a decrease in the level of nucleotide metabolism in Jurkat cells. In conclusion, increased citrate levels resulting from mitochondrial fusion significantly impair the ability of HIV to infect cells, which may due to regulate nucleotide metabolism
研究领域:
免疫学
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病毒学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Arthritis & Rheumatology
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2025
·
IF 10.9
Jin-Fen Ma,Ting Xu,Hao-Xian Zhu,Xiao-Min Chen,Liang Li,Zhi-Bin Zhao,Liwei Lu,Yang Li,Zhe-Xiong Lian,Cai-Yue Gao
Objective Activated T cells play a pivotal pathogenic role in the progression of Sjögren disease (SjD); however, there are currently no targeted therapies specifically designed to address them. This study aims to identify pathogenic CD8 + T cells in SjD and develop targeted therapeutic strategies. Methods Il12b-/-Il2ra-/- mice, a murine model for overlapping primary biliary cholangitis and SjD, were employed in this study. Pathogenic CD8 + T cells were identified through single-cell RNA sequencing and flow cytometry analyses of samples from both patients with SjD and relevant murine models. Shared T cell receptor analysis was conducted to trace the potential precursors of pathogenic CD8 + T cells. The efficacy of PD-1-targeted chimeric antigen receptor (CAR)–T cell therapy was evaluated through the assessment of salivary gland secretory function, immunologic profiles, and histopathological changes in the murine model. Results We identified PD-1 as a comprehensive marker of clonally expanded and activated pathogenic CD8 + T cells in the salivary glands and peripheral tissues. Flow cytometry further confirmed the activation phenotype and cytotoxicity of PD-1 + CD8 + T cells in the salivary glands of patients with SjD. Notably, the number of PD-1 + CD8 + T cells in the labial glands positively correlated with disease activity in patients with SjD. These findings highlight the therapeutic potential of depleting PD-1 + CD8 + T cells in SjD. Furthermore, PD-1-targeted CAR-T cell therapy significantly alleviated SjD symptoms in a murine model. Conclusion We identified the pathogenic role of PD-1 + CD8 + T cells in both patients with SjD and a murine model and demonstrated the efficacy of PD-1-targeted CAR-T cell therapy in SjD model mice. Our findings suggest a promising avenue for developing clinical therapeutic strategies for patients with SjD.
研究领域:
免疫学
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医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Xiejun Zhao,Xiangchuan Qin,Ruizhe Wang,Yawen Wang,Yinli He,Yuchen Wang,Kefeng Li,Peipei Zhang,Chen Yang,Menghan Wang,Yingtong Dong,Xue Shi,Jia Ma,Jiye Zhang,Xiaojiao Li
Inefficient priming, poor recruitment, and inadequate reinvigoration of T cells challenges the therapy of PD-L1-resistant tumors. Herein, a pH-responsive charge-reversal nanoplatform integrating coactivator-associated arginine methyltransferase 1 (CARM1) inhibitor (iCARM1) and poliovirus receptor siRNA (siPVR) is developed. Upon tumor penetration, iCARM1 released in tumor cells facilitates T cell priming by epigenetically activating cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling-mediated dendritic cell maturation. Meanwhile, in T cells, iCARM1 facilitates their recruitment by upregulating CXC-chemokine receptor 3 (CXCR3) expression. The released siPVR silences pvr to reinvigorate T cells. This epigenetic nanoagonist induces a robust immune response, dramatically suppresses tumor growth, metastasis, and relapse, and confers durable protection against secondary tumor challenge. Multiple PD-L1-resistant models demonstrate the broad applicability of this strategy. This study thus represents an innovative approach for facilitating multilevel T cell responses to combat PD-L1-resistant tumors.
研究领域:
癌症免疫治疗
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纳米医学
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表观遗传学
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分子生物学
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免疫学
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信号转导
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RNA干扰
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产品关联
DOI
PubMed
高影响因子
Applied Materials Today
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2020
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IF 8.352
Zhen Wang,Shuanghu Wang,Kun Liu,Dongmei Fu,Yicheng Ye,Junbin Gao,Lu Liu,Daniela A. Wilson,Yingfeng Tu,Fei Peng
Here we present an anti-CD3 loaded PLGA/ALG/CHI Mg micromotor systems, with degradable constituents and Mg-water reaction propulsion, thus ensuring a superior biocompatibility. Porous hydrogel formed by ALG/CHI offers high capacity of antigen loading, along with biocompatibility. By efficient loading of anti-human CD3 as an antigen and activating the calcium ion channel of Jurkat T cell, vital for immunotherapy, the motor system extends the application scope of micro/nanomotor systems from cargo (drug) delivery to interaction with the biointerface and immune activity modulation.
研究领域:
生物医学工程
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免疫学
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材料科学
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Xianghong Wang,Rong Lin,Dehai Li,Weiyuan Ye,Zhe Yang,Niujian Wu,Qiong Wen,Jingyi Tan,Chuanchuan Sun,Zhinan Yin,Hongyun Lu,Hengwen Yang
Previous studies have established that γδ T cells play a significant role in liver fibrosis. However, their specific functions and mechanisms in fibrotic liver tissue remain unclear. Using online microarray expression profiles, we observed that USF3 was upregulated in patients with liver fibrosis and was associated with immune cells. Additionally, increases in the expression of USF3 correlated with elevated levels of interferon-gamma (IFN-γ) in γδ T cells. However, the regulatory impact of USF3 on T cells, particularly in relation to fibrosis, has not been sufficiently elucidated. In this study, we employed conditional knockout mice (USF3 f/f ; CD2-cre) to investigate the role of USF3 in γδ T cells. The conditional knockout of USF3 resulted in an increase in both the number and proliferation of γδ T cells, which was associated with mTOR signaling pathway activation. The absence of USF3 significantly enhanced the expression of Eomes in γδ T cells, leading to an increase in IFN-γ production. Importantly, liver fibrosis was alleviated in USF3 conditional knockout mice, which was potentially linked to the enhanced proliferation of γδ T cells and the elevated expression of cytotoxic molecules, including IFN-γ. In summary, targeting USF3 in γδ T cells may represent a promising immunotherapeutic approach for liver fibrosis.
研究领域:
免疫学
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肝脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR CELL
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2024
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IF 14.5
Zhenxi Zhang,Yanting Yang,Yang Chen,Jingyu Su,Wenjing Du
The functional integrity of CD8 + T cells is closely linked to metabolic reprogramming; therefore, understanding the metabolic basis of CD8 + T cell activation and antitumor immunity could provide insights into tumor immunotherapy. Here, we report that ME2 is critical for mouse CD8 + T cell activation and immune response against malignancy. ME2 deficiency suppresses CD8 + T cell activation and anti-tumor immune response in vitro and in vivo . Mechanistically, ME2 depletion blocks the TCA cycle flux, leading to the accumulation of fumarate. Fumarate directly binds to DAPK1 and inhibits its activity by competing with ATP for binding. Notably, pharmacological inhibition of DAPK1 abolishes the anti-tumor function conferred by ME2 to CD8 + T cells. Collectively, these findings demonstrate a role for ME2 in the regulation of CD8 + T cell metabolism and effector functions as well as an unexpected function for fumarate as a metabolic signal in the inhibition of DAPK1.
研究领域:
免疫学
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肿瘤学
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代谢生物学
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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
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2019
·Vol. 37
·期 6
·598-603
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IF 2.804
Xia De-Yong,Jiang Qi-Min,Huang Wen-Yan,Yang Hong-Jun,Xue Xiao-Qiang,Jiang Li,Jiang Bi-Biao
The anionic polymerization of methyl methacrylate (MMA) was carried out using phosphazene base t -BuP 4 and ethyl acetate (EA) as the catalyst and the initiator, respectively. Gas chromatography (GC), size exclusion chromatography (SEC) measurements, and nuclear magnetic resonance (NMR) analyses were used to reveal the polymerization mechanism and to confirm the polymer structure. The results confirmed the proposed polymerization mechanism and the polymer structure, while the initiator efficiency was low. Meanwhile, the initiation by methoxy anion coming from hydrolysis of the ester bond in MMA was also observed. As a result, there is a marked deviation between the theoretical molecular weight and the measured molecular weight, and it is essential to carry out the polymerization at excessive dosage of t -BuP 4 for preparing polymers with narrow molecular weight distribution.
研究领域:
高分子化学
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材料科学
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产品关联
DOI
高影响因子
CELL
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2024
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IF 45.5
Shouyan Deng,Yibo Zhang,Huanbin Wang,Wenhua Liang,Lu Xie,Ning Li,Yuan Fang,Yiting Wang,Jiayang Liu,Hao Chi,Yufan Sun,Rui Ye,Lishen Shan,Jiawei Shi,Zan Shen,Yonggang Wang,Shuhang Wang,Jean-Philippe Brosseau,Feng Wang,Grace Liu,Yingfei Quan,Jie Xu
Cancer immunotherapy has transformed treatment possibilities, but its effectiveness differs significantly among patients, indicating the presence of alternative pathways for immune evasion. Here, we show that ITPRIPL1 functions as an inhibitory ligand of CD3ε, and its expression inhibits T cells in the tumor microenvironment. The binding of ITPRIPL1 extracellular domain to CD3ε on T cells significantly decreased calcium influx and ZAP70 phosphorylation, impeding initial T cell activation. Treatment with a neutralizing antibody against ITPRIPL1 restrained tumor growth and promoted T cell infiltration in mouse models across various solid tumor types. The antibody targeting canine ITPRIPL1 exhibited notable therapeutic efficacy against naturally occurring tumors in pet clinics. These findings highlight the role of ITPRIPL1 (or CD3L1, CD3ε ligand 1) in impeding T cell activation during the critical “signal one” phase. This discovery positions ITPRIPL1 as a promising therapeutic target against multiple tumor types.
研究领域:
免疫学
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肿瘤学
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医学
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DOI
PubMed
高影响因子
ACTA PHYSIOLOGIAE PLANTARUM
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2010
·Vol. 33
·期 4
·1271-1276
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IF 1.232
Guan Yajing,Hu Jin,Li Yongping,Ma Wenguang,Zheng Yunye
Counterfeit seeds cause a large loss in seed industry and crop production. Present study was undertaken to find a new anti-counterfeiting technology by labeling seeds with a fluorescent compound, safranine T (ST). Response surface analysis (RSA) experiment with two factors (ST concentration and seed soaking time) of 14 combinations was performed to investigate the ST effects on seed vigor and fluorescence showing in seedlings of two tobacco varieties, MS Yunyan 85 and Honghua Dajinyuan. After soaking in ST solutions, tobacco seeds were germinated for 16 days, then the germination index (GI), vigor index (VI), length of roots and shoots were determined. The optimum combinations of ST concentration and soaking time on GI, VI and length of shoots and roots were 0.57–0.69 mg/ml and 6.77–9.34 h for MS Yunyan 85 and 0.51–0.80 mg/ml and 5.81–7.39 h for Honghua Dajinyuan, respectively. Meanwhile, tobacco seedlings, treated with ST solutions from 0.3 to 1.5 mg/ml showed obviously fluorescence under illumination of green light. It suggests that soaking tobacco seeds in safranine T solution of suitable concentration can be used as a labeling technique for anti-counterfeiting in tobacco seeds.
研究领域:
种子科学
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农业生物技术
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植物生理学
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分析化学
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作物生产
✓ 已验证
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2020
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IF 4.872
Ruifen Kang,Aneela Perveen,Chunmei Li
T-2 toxin is a kind of group A trichothecenes mycotoxins , frequently detected in various foods and feeds, having high toxic effects on both humans and animals. The present study aims to investigate the toxic effects of T-2 toxin exposure to ICR mice during pregnancy and lactation on liver glycolipid metabolism of young mice. The pregnant mice were given 0, 0.005 and 0.05 mg of T-2 toxin/kg bw daily through oral gavage from late gestation (GD 14) to the lactation (LD 21). Liver and serum samples of the young mice were collected on postnatal day 21 (PND 21), PND 28 and PND 56. The results showed that T-2 toxin increased the contents of triglycerides (TG), total cholesterol (T-CHO) and glucose in serum of young mice on PND 21 and PND 28. In addition, obvious lipid droplets of liver in T-2 toxin treatment groups were observed, especially in 0.05 mg group of PND 21and PND 28. Compared with the control group, T-2 treatment also increased the expressions of genes associated with liver glycolipid metabolism, such as PEPCK , Glut2 , Fas , Acox1 , Hmgcr , PPARα , Srebp1 and CD36 . These results demonstrated T-2 toxin exposure to pregnant mice could cause liver glycolipid metabolism disruption in the young mice and the toxic effects weakened on PND 56.
研究领域:
毒理学
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营养学
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2016
·Vol. 184
·期 3
·687-691
·
IF 4.831
Hui Pan,Gao Wenyue,Nsabimana Jacques,Li Yunhui,Yang Xiuyun,Gao Ying,Shao Jing,Xu Guobao
The authors describe a method for amperometric determination of chloramine-T that is based on the indirect detection of chloramine-T by detecting p -quinone imine ( p -QI) that is generated by oxidation of p -aminophenylboronic acid by chloramine-T. p -QI can be detected with excellent selectivity and at low potential by using a glassy carbon electrode. Hence, the method displays attractive features such as high sensitivity, wide detection range and excellent selectivity. The electrode has two linear responses in the 50 nM to 100 μM concentration range and a 6 nM detection limit. Compared to other electrochemical methods, this assay has a detection limit that is better by three orders of magnitude. The relative standard deviation is 3.4% for the determination of 10 μM of the medical chloramine-T sample, and the recovery of a samples containing chloramine-T at a level of 10 μM is 115%.
Highly sensitive electrochemical detection of chloramine-T is achieved based on the reaction of chloramine-T with p -aminophenylboronic acid with a detection limit of 6 nM.
研究领域:
分析化学
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医学检测
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电化学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Jiaxiang Hu,Qingmiao Shi,Chen Xue,Qingqing Wang
Accumulating evidence suggests that berberine (BBR) exhibits anti-cancer effects in hepatocellular carcinoma (HCC). However, the mechanisms by which BBR regulates the immunological microenvironment in HCC has not been fully elucidated. In this study, a mouse model of orthotopic HCC is established and treated with varying doses of BBR. BBR showed effectiveness in reducing tumor burden in mice with HCC. Cytometry by time-of-flight depicted the alterations in the tumor immune landscape following BBR treatment, revealing the enhancement in the T lymphocytes effector function. In particular, BBR decreased the proportion of TCRb hi PD-1 hi CD69 + CD27 + effector CD8 + T lymphocytes and increased the proportion of Ly6C hi TCRb + CD69 + CD27 + CD62L + central memory CD8 + T lymphocytes. Single-cell RNA sequencing further elucidates the effects of BBR on transcriptional profiles of liver immune cells and confirms the phenotypical heterogeneity of T lymphocytes in HCC immune microenvironment. Additionally, it is found that BBR potentially regulated the antitumor immunity in HCC by modulating the receptor-ligand interaction among immune cells mediated by cytokines. In summary, the findings improve the understanding of BBR's impact on protecting against HCC, emphasizing BBR's role in regulating intrahepatic T cell heterogeneity. BBR has the potential to be a promising therapeutic strategy to hinder the advancement of HCC.
研究领域:
肿瘤学
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免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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