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Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

Signal Transduction and Targeted Therapy 2024年第3期9卷 1230-1243页

作者： Jun Zhou Jiaqi Liu Bingjing Wang Nan Li Juan Liu Yanmei Han Xuetao Cao institute of immunology Zhejiang University School of MedicineHangzhou 310058China National key laboratory of Immunity and Inflammation Institute of ImmunologyNaval Medical UniversityShanghai 200433China Department of immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100005China institute of immunology College of Life SciencesNankai UniversityTianjin 300071China

Memory CD8+T cell generation is crucial for pathogen elimination and effective vaccination against *** cellular and molecular circuitry that underlies the generation of memory CD8+T cells remains *** can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune *** we report that eosinophils are required for the generation of memory CD8+T cells by inhibiting CD8+T cell ***-deficient mice display significantly impaired memory CD8+T cell response and weakened resistance against Listeria monocytogenes(L.m.)***,eosinophils secrete interleukin-4(IL-4)to inhibit JNK/Caspase-3 dependent apoptosis of CD8+T cells upon *** in ***,active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+T cell apoptosis during early stage of *** in *** transfer of wild-type(WT)eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+T cell memory ***,our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+T cell memory and enhances immune defense against *** study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

关键词： impaired immunity spleen

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Progress in gut microbiota-host interaction

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Science China(Life Sciences) 2024年第5期67卷 851-853页

作者： Changtao Jiang Department of immunology School of Basic Medical SciencesNHC Key Laboratory of Medical ImmunologyPeking UniversityBeijing 100191China

Recently,the gut microbiota has been recognized as a novel endocrine organ in the human *** produces various bioactive metabolites and participates in metabolic *** addition,the gut microbiota is involved in the metab... 详细信息

关键词： metabolism drugs processes

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PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3049-3067页

作者： Jianming Yang Yawen Xiao Ningning Zhao Geng Pei Yan Sun Xinyu Sun Kaiyuan Yu Chunhui Miao Ran Liu Junqiang Lv Hongyu Chu Lu Zhou Bangmao Wang Zhi Yao Quan Wang key laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Institute of ImmunologyState Key Laboratory of Experimental Hematologythe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsDepartment of ImmunologySchool of Basic Medical SciencesTianjin Institute of Urologythe Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Cellular and Molecular ImmunologyTianjin Medical UniversityTianjin 300070China Department of Pathology Tianjin Medical University Cancer Institute and Hospital/National Clinical Research Center of Cancer/Key Laboratory of Cancer Prevention and TherapyTianjin/Tianjin’s Clinical Research Center of CancerTianjin 30060China Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300070China

The mucosal barrier is crucial for intestinal homeostasis,and goblet cells are essential for maintaining the mucosal barrier *** proviral integration site for Moloney murine leukemia virus-1(PIM1)kinase regulates multiple cellular functions,but its role in intestinal homeostasis during colitis is ***,we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models,in the presence of intestinal *** PIM1 leads to decreased goblet cells,thus impairing resistance to colitis and colitis-associated colorectal cancer(CAC)in ***,PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling ***,PIM1 interacts with histone deacetylase 2(HDAC2)and downregulates its level via phosphorylation,thereby altering the epigenetic profiles of Wnt signaling pathway ***,these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis,which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

关键词： PIM1 HDAC2 Goblet cell Gut microbiota Intestinal homeostasis Epigenetic modification Ulcerative colitis CAC

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Nutritional competition within tumor microenvironment dictates anti-tumor immunity

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National Science Review 2024年第2期11卷 98-100页

作者： Yankang Fei Xuetao Cao Juan Liu National key laboratory of Immunity and Inflammation Institute of Immunology Naval Medical University Department of immunology Chinese Academy of Medical Sciences institute of immunology College of Life Sciences Nankai University

The crosstalk between metabolism and immunity has emerged as an essential regulator of tumor immune escape, and targeting immunometabolic pathways holds great potential for cancer immunotherapy [1]. Abnormal metabolic...

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Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia

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Virologica Sinica 2024年第1期39卷 31-43页

作者： Dongyan Zhang Xiulin Wu Xing Xue Wenshi Li Ping Zhou Zhao Lv Kexin Zhao Fan Zhu State key laboratory of Virology and Department of medical Microbiology School of Basic Medical SciencesWuhan UniversityWuhan430071China Hubei Province key laboratory of Allergy&immunology Wuhan UniversityWuhan430071China

Human endogenous retroviruses(HERVs)are remnants of retroviral infections in human germline cells from millions of years *** these,ERVW-1(also known as HERV-W-ENV,ERVWE1,or ENVW)encodes the envelope protein of the HERV-W family,which contributes to the pathophysiology of ***,neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with ***,our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset(GSE53987)were mainly related to ferroptosis and its associated *** data demonstrated significantly lower expression levels of ferroptosis-related genes,particularly Glutathione peroxidase 4(GPX4)and solute carrier family 3 member 2(SLC3A2),in schizophrenia patients compared to normal *** in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in *** indicated that ERVW-1 increased iron levels,malondialdehyde(MDA),and transferrin receptor protein 1(TFR1)expression while decreasing glutathione(GSH)levels and triggering the loss of mitochondrial membrane potential,suggesting that ERVW-1 can induce *** research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter ***,Ferrostatin-1(Fer-1),the ferroptosis inhibitor,reversed the iron accumulation and mitochondrial membrane potential loss,as well as restored the expressions of ferroptosis markers GSH,MDA,and TFR1 induced by *** conclusion,ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2,revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.

关键词： ERVW-1 Glutathione peroxidase 4(GPX4) Solute carrier family 3 member 2(SLC3A2) Ferroptosis Schizophrenia

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Decreased LDHB expression in breast tumor cells causes NK cell activation and promotes tumor progression

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Cancer Biology & Medicine 2024年第6期21卷 513-540页

作者： Zhihong Luo Xiaohua Huang Xinyi Xu Kefeng Wei Yi Zheng Ke Gong Wenhua Li Hubei key laboratory of Cell Homeostasis College of Life SciencesWuhan UniversityWuhan 430072China Wuhan University Shenzhen Research institute Shenzhen 518057China Central laboratory University of Chinese Academy of Sciences-Shenzhen HospitalShenzhen 518107China Hubei Province key laboratory of Allergy and immunology and Department of immunology School of Basic Medical SciencesWuhan UniversityWuhan 430071China

Objective: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B(LDHB) has been detected in breast cancer but the function of LDHB remains ***: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer(NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell ***: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some ***: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regula

关键词： Breast cancer lactate dehydrogenase B lactic acid NK cells tumor immunity

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Naturally occurring PA^(E206K)point mutation in 2009 H1N1 pandemic influenza viruses impairs viral replication at high temperatures

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Virologica Sinica 2024年第1期39卷 71-80页

作者： Mengmeng Cao Qiannan Jia Jinghua Li Lili Zhao Li zhu Yufan Zhang Shan Li Tao Deng National institute of Pathogen Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100730China CAS key laboratory of Pathogen Microbiology and immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101China

The emergence of influenza virus A pandemic H1N1 in April 2009 marked the first pandemic of the 21st *** this study,we observed significant differences in the polymerase activities of two clinical 2009 H1N1 influenza A virus isolates from Chinese and Japanese *** comparison of the three main protein subunits(PB2,PB1,and PA)of the viral RNA-dependent RNA polymerase complex and subsequent mutational analysis revealed that a single amino acid substitution(E206K)was responsible for the observed impaired replication *** in vitro experiments showed that presence of PAE206K decreased the replication of influenza A/WSN/33 virus in mammalian cells and a reduction in the virus’s pathogenicity in *** studies revealed that PAE206K is a temperature-sensitive mutant associated with the inability to transport PB1–PA complex to the nucleus at high temperature(39.5℃).Hence,this naturally occurring variant in the PA protein represents an ideal candidate mutation for the development of live attenuated influenza vaccines.

关键词： H1N1 Influenza A virus Polymerase acidic protein Point mutation Viral replication

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Nano polystyrene microplastics could accumulate in Nile tilapia(Oreochromis niloticus):Negatively impacts on the intestinal and liver health through water exposure

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Journal of Environmental Sciences 2024年第3期137卷 604-614页

作者： Di Wu Xing Lu Li-Xue Dong Juan Tian Jin Deng Lei Wei Hua Wen Shan Zhong Ming Jiang School of Basic medical Sciences Wuhan UniversityWuhan 430071China key laboratory of Freshwater Biodiversity Conservation Ministry of Agriculture and Rural AffairsYangtze River Fisheries Research InstituteChinese Academy of Fishery SciencesWuhan 430223China Hubei Province key laboratory of Allergy and immunology Wuhan 430071China

Microplastics(MPs)have become a significant concern for their potential ***,the correlation between the size of plastic particles and their toxicity remains ***,we investigate the toxic effects of different sizes(80 nm,800 nm,8μm and 80μm)polystyrene MPs(PS-MPs)on the model organism Nile tilapia(Oreochromis niloticus).The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body.H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm *** U labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm *** gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm *** analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm *** conclusion,this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver *** the above lay the foundation for further study on the pathological damage of MPs to other organisms.

关键词： Microplastics(MPs) Intestinal toxicity Liver toxicity Gut microbiome Lipid metabolism

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γδT cells:Major advances in basic and clinical research in tumor immunotherapy

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Chinese medical Journal 2024年第1期137卷 21-33页

作者： Yueqi Zhao Peng Dong Wei He Jianmin Zhang Hui Chen Department of immunology CAMS Key Laboratory for T Cell and ImmunotherapyState Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeBeijing 100005China Changzhou Xitaihu institute for Frontier Technology of Cell Therapy ChangzhouJiangsu 213000China Haihe laboratory of Cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China

γδT cells are a kind of innate immune T *** have not attracted sufficient attention because they account for only a small proportion of all immune cells,and many basic factors related to these cells remain ***,in recent years,with the rapid development of tumor immunotherapy,γδT cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex(MHC)*** increasing number of basic studies have focused on the development,antigen recognition,activation,and antitumor immune response ofγδT ***,γδT cell-based immunotherapeutic strategies are being developed,and the number of clinical trials investigating such strategies is *** review mainly summarizes the progress of basic research and the clinical application ofγδT cells in tumor immunotherapy to provide a theoretical basis for further the development ofγδT cell-based strategies in the future.

关键词： Gamma-delta T-cells T cell receptor CD1a Tumor immunotherapy Receptors,chimeric antigen Vδ1 cells αβT cells

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Not to be and how not to be:the questions of Tregs controlled by RIPK1

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Cellular & Molecular immunology 2024年第2期21卷 205-206页

作者： Zhengcai Peng Huiyuan Zhang Hongbo Hu Center for immunology and Hematology Department of Biotherapy and Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China Chongqing International institute for immunology Chongqing401338China

Millions of cells undergo daily cell death,a process essential for maintaining physiological homeostasis and *** forms of cell death,such as apoptosis,necroptosis,ferroptosis and pyroptosis,have been extensively studied for their distinct biological functions[1,2].Generally,programmed cell death,like apoptosis,is considered physiological and results in little to no inflammatory response.

关键词： death homeostasis pathogenesis

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