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Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing

Cellular & Molecular immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin Ying Liu Feng Tian Ying Yu Pengfei Yuan Shuaixin Gao Thomas S.Fulford Adam P.Uldrich Catherine C.L Wong Wensheng Wei biomedical Pioneering Innovation center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina center for Precision Medicine Multi-Omics research Peking University Health Science CenterPeking University100191BeijingChina department of microbiology and immunology at the Peter Doherty Institute for Infection and Immunity The University of MelbourneParkvilleVIC3010Australia Cancer immunology Program Peter MacCallum Cancer CentreMelbourneVICAustralia State Key Laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate *** our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer *** found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T *** coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX ***,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer *** our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T ***,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.

关键词： Butyrophilin Vγ9Vδ2 T-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like Pyrophosphate metabolite Immunotherapy

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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & Molecular immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA Medical center ChicagoILUSA department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA department of microbiology and immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK department of biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Is Veillonella a unique marker of physical exercise?Commentary on:

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Journal of Sport and Health Science 2024年第5期13卷 682-684页

作者： Viktor Bielik Ivan Hric Riadh Hammami department of Biological and Medical Science Faculty of Physical Education and SportComenius University in BratislavaBratislava 81469Slovakia department of Molecular Biology Faculty of Natural SciencesComenius University in BratislavaBratislava 84215Slovakia biomedical research center Institute of Clinical and Translational ResearchSlovak Academy of SciencesBratislava 84505Slovakia School of Nutrition Sciences Faculty of Health SciencesUniversity of OttawaOttawaON K1N 6N5Canada department of Biochemistry Microbiology and ImmunologyFaculty of MedicineUniversity of OttawaOttawaON K1N 6N5Canada

In 2020,Kostic1 published commentary on the bacterial genus Veillonella associated with the interaction between the intestinal microbiota and skeletal *** then,novel perspectives on the bidirectional gut-muscle communication axis have gained a lot of *** purpose of this commentary is to explore some of the challenging issues presented in Scheiman et al.

关键词： skeletal gained

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A novel method for identifying SARS-CoV-2 infection mutants via an epitope-specific CD8^(+)T cell test

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Biosafety and Health 2024年第3期6卷 143-152页

作者： Congling Qiu Bo Peng Chanchan Xiao Pengfei Chen Lipeng Mao Xiaolu Shi Zhen Zhang Ziquan Lv Qiuying Lv Xiaomin Zhang Jiaxin Li Yanhao Huang Qinghua Hu Guobing Chen Xuan Zou Xiaofeng Liang department of Public Health and Preventive Medicine School of MedicineJinan UniversityKangtai Biological Vaccine Industry Research Institute/Disease Prevention and Control Institute of Jinan UniversityGuangzhou 510632China Shenzhen center for Disease Control and Prevention Shenzhen 518020China department of microbiology and immunology Institute of Geriatric ImmunologySchool of MedicineJinan UniversityGuangzhou 510632China Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan University) Ministry of EducationGuangzhou 510632China The Sixth Affiliated Hospital Jinan UniversityGuangzhou 510632China department of Systems biomedical Sciences School of MedicineJinan UniversityGuangzhou 510632China microbiology Laboratory Shenzhen Center for Disease Control and PreventionShenzhen 518020China department of Communicable Diseases Control and Prevention Shenzhen Center for Disease Control and PreventionShenzhen 518020China Central Laboratory Shenzhen Center for Disease Control and PreventionShenzhen 518020China

Since the outbreak of the coronavirus disease 2019(COVID-19)epidemic in 2019,the public health system has faced enormous *** the individuals who test positive for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a key step for interrupting chains of transmission of SARS-CoV-2 and reducing COVID-19-associated *** the increasing of asymptomatic infections,it is difficult to track asymptomatic infections through epidemiological surveys and virus whole-genome ***,due to the cross-reactivity of neutralizing antibodies produced by multiple virus subtypes,neutralizing antibody detection cannot be used to determine whether an individual has a history of infection with a specific subtype of *** recruited 4 human leukocyte antigen A2(HLA-A2)infections,15 individuals who received three doses of inactivated vaccines,and 30 breakthrough infections after vaccination and discussed a case-tracking approach to detect epitope-specific CD8^(+)T cells in the peripheral blood of close contacts,including accurate HLA typing based on ribonucleic acid(RNA)-sequencing and flow cytometry data and the comparison and characterization of SARS-CoV-2 HLA-A2 and HLA-A24 epitope-specific CD8^(+)T *** individuals who received three doses of inactivated vaccine,we observed that the CD8^(+)T cell specificity for ancestral epitopes was significantly higher than for mutated epitopes,and the fold change of CD8^(+)T cells corresponding to mutated epitopes relative to ancestral epitopes was less than *** enzyme-linked immunospot(ELISpot)results further validate this *** study forms a“method for understanding the infection history of SARS-CoV-2 subtypes based on the proportion of epitope-specific CD8^(+)T cells in the peripheral blood of subjects”,covering up to 46%of the population,including HLA-A2+and HLA-A24+donors,providing a novel method for SARS-CoV-2 infected case tracing.

关键词： Asymptomatic coronavirus disease 2019 (COVID-19) Epitopes Specific CD8^(+)T cell ELISpot

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Weakened tanning ability is an important mechanism for evolutionary skin lightening in East Asians

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Journal of Genetics and Genomics 2024年第7期51卷 703-713页

作者： Youwei Pu Siyu Pu Yanyan Chen Qinghong Kong Xuyang Liu Qi Zhao Ke Xu Jiuming Liu Mengyuan Li Xiaoyu Xu Xiaoyang Qiao Bing Su Jing Chen Zhaohui Yang Tianjian Laboratory of Advanced biomedical Sciences Academy of Medical ScienceZhengzhou UniversityZhengzhouHenan 450052China department of Pediatric Surgery and Laboratory of Pediatric Surgery West China HospitalSichuan UniversityChengduSichuan 610041China Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines Zunyi Medical UniversityZunyiGuizhou 563000China Yunnan Key Laboratory of primate biomedical research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan 650500China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan 650223China

The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude *** Asians are ideal populations for studying skin color evolution because of the complex environment of East ***,we report a strong selection signal for the pigmentation gene phenylalanine hydroxylase(PAH)in light-skinned Han Chinese *** intron mutation rs10778203 in PAH is enriched in East Asians and is significantly associated with skin color of the back of the hand in Han Chinese males(P<0.05).In vitro luciferase and transcription factor binding assays show that the ancestral allele of rs10778203 could bind to SMAD2 and has a significant enhancer activity for ***,the derived T allele(the major allele in East Asians)of rs10778203 decreases the binding activity of transcription factors and enhancer ***,the derived T allele of rs10778203 shows a weaker ultraviolet radiation response in A375 cells and zebrafish ***,rs10778203 decreases melanin production in transgenic zebrafish embryos after ultraviolet B(UVB)***,PAH is a potential pigmentation gene that regulates skin tanning *** selection has enriched the adaptive allele,resulting in weakened tanning ability in East Asians,suggesting a unique genetic mechanism for evolutionary skin lightening in East Asians.

关键词： East Asians PAH Skin pigmentation Natural selection Genetic adaptation

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Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1147-1164页

作者： Yan Guo Pan Xiang Xiaojiao Sun Wei Liu Jiafeng Zhou Bin Yin Lin Hou Boqin Qiang Huiliang Li Pengcheng Shu Xiaozhong Peng department of Molecular Biology and Biochemistry Institute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina State Key Laboratory of Common Mechanism research for Major Diseases Beijing 100005China Wolfson Institute for biomedical research University College LondonGower StreetLondon WC1E 6BTUK Chinese Institute for Brain research Beijing 102206China State Key Laboratory of Respiratory Health and Multimorbidity Beijing 100005China Institute of Laboratory Animal Science Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits,and this process requires the proper recruitment of adaptor molecules to selectively activate downstream ***,we identified that DOK6,a member of the Dok(downstream of tyrosine kinases)family,is required for the maintenance of peripheral axons,and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice,manifested as impaired sensory,abnormal posture,paw deformities,blocked nerve conduction,and ***,Dok6 is highly expressed in peripheral neurons but not in Schwann cells,and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding,axon destruction,and hindered retrograde axonal ***,DOK6 acts as an adaptor protein for selectivitymediated neurotrophic signal transduction and retrograde transport for TrkC and Ret but not for TrkA and ***6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation,including MAP1B,Tau and Dynein for axonal transport,and specifically activates the downstream ERK1/2 kinase pathway to maintain axonal survival and *** finding provides new clues to potential insights into the pathogenesis and treatment of hereditary peripheral neuropathies and other degenerative diseases.

关键词： impaired restrain peripheral

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Fli1 acts in parallel with Pu.1 to control macrophage and neutrophil fate in zebrafish

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Journal of Genetics and Genomics 2024年第3期51卷 359-362页

作者： Ao Zhang Jingao Lu Shachuan Feng Huapeng Yu Tao Yu Shizheng Zhao Kemin Chen Zhibin Huang Jin Xu Jianan Y.Qu Zilong Wen Division of Life Science Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhouGuangdong 510006China department of immunology and microbiology School of Life ScienceSouthern University of Science and TechnologyShenzhenGuangdong 518055China biomedical research Institute Shenzhen Peking University-Hong Kong University of Science and Technology Medical CenterShenzhenGuangdong 518036China department of Electronic and Computer Engineering Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Greater Bay biomedical Innocenter Shenzhen Bay LaboratoryShenzhenGuangdong 518067China

Macrophages and neutrophils are key components of myeloid cells and play critical roles in innate immune responses,organ formation,and tissue *** integrity of their functions heavily relies on the generation of a proper number of mature macrophages and neutrophils through embryonic and adult *** mammalian adult myelopoiesis,oligopotent common myeloid progenitors(CMPs)are known to be the earliest myeloid progenitors,which give rise to granulocyte-macrophage progenitors(GMPs),subsequently differentiate into unipotent neutrophil and macrophage precursors,and finally,mature macrophages and neutrophils(Orkin and Zon,2008).In contrast,the ontogeny of embryonic myelopoiesis and the mechanism underlying the formation of macrophages and neutrophils remainless understood.

关键词： fish macrophage homeostasis

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Fight or flee,a vital choice for Clostridioides difficile

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mLife 2024年第1期3卷 14-20页

作者： Ji Zeng Sshuying Fang Jinquan Guo Min Dong Guo-Bao Tian Liang Tao School of biomedical and Pharmaceutical Sciences Guangdong University of TechnologyGuangzhouChina department of Brest Surgery Panyu Central Hospital.GuangzhouChina department of microbiology Harvard Medical SchoolBostonMassachusettsUSA department of Urology Boston Children's HospitalHarvard Medical SchoolBostonMassachusettsUSA department of microbiology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouChina Advanced Medical Technology center The First Affiliated HospitalZhongshan School of MedicineSun Yat-sen UniversityGuangzhouChina Key Laboratory of Tropical Diseases Control(Sun Yat-sen University) Ministry of EducationGuangzhouChina School of Medicine Xizang Minzu UniversityXianyangChina center for Infectious Disease research Westlake Laboratory of Life Sciences and BiomedicineWestlake UniversityHangzhouChina research center for Industries of the Future School of Life SciencesWestlake UniversityHangzhouChina

Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every *** symptoms range from mild diarrhea to life-threatening damage to the *** and recurrence of *** infection(CDl)are mediated by the metabolically dormant spores,while the virulence of *** is mainly due to the two large clostridial toxins,TcdA and *** toxins or forming spores are two different strategies for *** to cope with harsh environmental *** is of great significance to understand the molecular mechanisms for *** to skew to either of the cellular ***,we summarize the current understanding of the regulation and connections between toxin production and sporulation in *** and further discuss the potential solutions for yet-to-be-answered questions.

关键词： C.difficile sporulation TcdA TcdB toxin production

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High-yield and rapid isolation of extracellular vesicles by flocculation via orbital acoustic trapping:FLOAT

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Microsystems & Nanoengineering 2024年第1期10卷 313-323页

作者： Joseph Rufo Peiran Zhang Zeyu Wang Yuyang Gu Kaichun Yang Joseph Rich Chuyi Chen Ruoyu Zhong Ke Jin Ye He Jianping Xia Ke Li Jiarong Wu Yingshi Ouyang Yoel Sadovsky Luke P.Lee Tony Jun Huang department of Mechanical Engineering and Materials Science Duke UniversityDurhamNCUSA department of biomedical Engineering Duke UniversityDurhamNCUSA department of Obstetrics Gynecologyand Reproductive SciencesMagee-Womens Research InstituteUniversity of PittsburghPittsburghPAUSA department of microbiology and Molecular Genetics School of MedicineUniversity of PittsburghPittsburghPAUSA Renal Division and Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA department of Bioengineering Department of Electrical Engineering and Computer ScienceUniversity of CaliforniaBerkeleyBerkeleyCAUSA department of Biophysics Institute of Quantum BiophysicsSungkyunkwan UniversitySuwonKorea

Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various ***,challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low ***,we report a high-yield(>90%)and rapid(center of the *** demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein,addressing a significant obstacle in the development of EV-based liquid *** to its high-yield nature,FLOAT reduces biofluid starting volume requirements by a factor of 100(from 20 mL to 200µL),demonstrating its promising potential in point-of-care diagnostics.

关键词： trapping utilize separating

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Vlultifunctional immune responses of HMBPP-specific Jy2Vδ2 T cells in M. tuberculosis and other infections

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Cellular & Molecular immunology 2013年第1期10卷 58-64页

作者： Zheng W Chen department of microbiology and immunology Center for Primate Biomedical Research University of Illinois College of Medicine Chicago chicago IE 60612: USA

Vy2Vδ2 T （also known as Vy9Vδ2 T） cells exist only in primates, and in humans represent a major yδ T-cell sub-population in the total population of circulating yδ T cells. Results from recent studies suggest that while （E）-4-hydroxy-3-methyl-but-2-enyl pyrophosphate （HMBPP） phosphoantigen from Mycobacterium tuberculosis （Mtb） and other microbes activates and expands primate Vy2Vδ2 T cells, the Vy2Vδ2 T-cell receptor （TCR） recognizes and binds to HMBPP on antigen-presenting cells （APC）. In response to HMBPP stimulus, Vy2V82 TCRs array to form signaling-related nanoclusters or nanodomains during the activation of Vy2V82 T cells. Primary infections with H MBPP-producing pathogens drive the evolution of multieffector functional responses in Vy2Vδ2 T cells, although Vy2V82 T cells display different patterns of responses during the acute and chronic phases of Mtb infection and in other infections. Expanded Vy2Vδ2 T cells in primary Mtb infection can exhibit a broader TCR repertoire and a greater clonal response than previously assumed, with different distribution patterns of Vδ,2Vδ2 T-cell clones in lymphoid and non-lymphoid compartments. Emerging in vivo data suggest that HMBPP activation of Vy2W2 T cells appears to impact other immune cells during infection.

关键词： (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate yδ T cell HMBPP human infection phosphoantigen T cell receptor T-cell response tuberculosis

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