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Peripheral memory T cells specific for Arginase-1

Cellular & Molecular Immunology 2019年第8期16卷 718-719页

作者： Evelina Martinenaite Shamaila Munir Ahmad inge marie svane Mads Hald Andersen Center for Cancer Immune Therapy(CCIT) Copenhagen University HospitalHerlevDenmark Department of Immunology and Microbiology University of CopenhagenCopenhagenDenmark

Increased arginase-1(Arg-1)activity is one of the common mechanisms of immune inhibition in patients with ***-1 is an enzyme catalyzing the first step in L-arginine metabolism and is expressed by various immunosuppressive myeloid cells as well as by cancer ***-1-associated deprivation of L-arginine downregulates the expression of the T cell receptorζchain and decreases cytokine production and proliferation of activated T cells.

关键词： metabolism Arg cytokine

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Cytotoxic T cells isolated from healthy donors and cancer patients kill TGFβ-expressing cancer cells in a TGFβ-dependent manner

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Cellular & Molecular Immunology 2021年第2期18卷 415-426页

作者： Morten Orebo Holmström Rasmus Erik Johansson Mortensen Angelos Michail Pavlidis Evelina Martinenaite Stine Emilie Weis-Banke Mia Aaboe-Jørgensen Simone Kloch Bendtsen Özcan Met Ayako Wakatsuki Pedersen Marco Donia inge marie svane Mads Hald Andersen Department of Oncology National Center for Cancer Immune TherapyCopenhagen University HospitalHerlevDenmark IO Biotech ApS CopenhagenDenmark Institute for Immunology and Microbiology Copenhagen UniversityCopenhagenDenmark

Transforming growth factor-beta(TGFβ)is a highly potent immunosuppressive *** TGFβis a tumor suppressor in early/premalignant cancer lesions,the cytokine has several tumor-promoting effects in advanced cancer;abrogation of the antitumor immune response is one of the most important tumor-promoting *** several immunoregulatory mechanisms have recently been shown to be targets of specific T cells,we hypothesized that TGFβis targeted by naturally occurring specific T cells and thus could be a potential target for immunomodulatory cancer ***,we tested healthy donor and cancer patient T cells for spontaneous T-cell responses specifically targeting 3820-mer epitopes derived from TGFβ*** identified numerous CD4^(+)and CD8^(+)T-cell responses against several epitopes in TGFβ.Additionally,several ex vivo responses were *** enriching specific T cells from different donors,we produced highly specific cultures specific to several TGFβ-derived *** CD8^(+)T-cell clones specific for both a 20-mer epitope and a 9-mer HLA-A2 restricted killed epitope peptide were pulsed in HLA-A2+target cells and killed the HLA-A2+cancer cell lines THP-1 and ***,stimulation of THP-1 cancer cells with cytokines that increased TGFβexpression increased the fraction of killed *** conclusion,we have shown that healthy donors and cancer patients harbor CD4^(+)and CD8^(+)T cells specific for TGFβ-derived epitopes and that cytotoxic T cells with specificity toward TGFβ-derived epitopes are able to recognize and kill cancer cell lines in a TGFβ-dependent manner.

关键词： Immune regulation TGFbeta cancer T cells adaptive immunity

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Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

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World Journal of Gastroenterology 2024年第4期30卷 332-345页

作者： Yi-Jie Li Brittney O Baumert Nikos Stratakis Jesse A Goodrich Hao-Tian Wu Jing-Xuan He Yin-Qi Zhao Max T Aung Hong-Xu Wang Sandrah P Eckel Douglas I Walker Damaskini Valvi Michele A La Merrill Justin R Ryder Thomas H inge Todd Jenkins Stephanie Sisley Rohit Kohli Stavra A Xanthakos Andrea A Baccarelli Rob McConnell David V Conti Lida Chatzi Department of Population and Public Health Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90032United States Barcelona Institute of Global Health Barcelona Institute of Global HealthBarcelona 08036Spain Department of Environmental Health Sciences Mailman School of Public HealthColumbia UniversityNew YorkNY 10032United States Gangarosa Department of Environmental Health Rollins School of Public HealthEmory UniversityAtlantaGA 30329United States Department of Environmental Medicine and Public Health Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Department of Environmental Toxicology University of CaliforniaDavisCA 95616United States Department of Surgery Lurie Children’s Hospital of ChicagoChicagoIL 60611United States Northwestern University Feinberg School of Medicine Northwestern UniversityChicagoIL 60611United States Division of Biostatistics and Epidemiology Cincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States Department of Pediatrics University of Cincinnati College of MedicineCincinnatiOH 45229United States Department of Pediatrics Children’s Nutrition Research Center USDA/ARSBaylor College of MedicineHoustonTX 77030United States Department of Gastroenterology Children’s Hospital Los AngelesLos AngelesCA 90027United States Division of Gastroenterology Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and *** ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with *** microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains *** analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in *** To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with *** This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery ***-operative core liver biopsies were collected from participants and used to characterize histological features of *** samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq *** examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key *** Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of *** We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with ***,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,***,16 miRNAs were associated with two or more histological features of *** those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and posi

关键词： MicroRNA Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Liver fibrosis Lobular inflammation Ballooning degeneration

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Mitochondrial Perturbation Negatively Affects Auxin Signaling

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Molecular Plant 2014年第7期7卷 1138-1150页

作者： Pavel Ivanov Kerchev inge De Clercq Jordi Denecker Per Muihlenbock Robert Kumpf Long Nguyen Dominique Audenaert Wim Dejonghe Frank Van Breusegem Department of Plant Systems Biology VIB Ghent University B-9052 Gent Belgium Department of Plant Biotechnology and Bioinformatics Ghent University B-9052 Gent Belgium Present address: Department of Plant Protection Biology Swedish University of Agricultural Sciences SE-230 53 Alnarp Sweden VlB Compound Screening Facility B-9052 Gent Belgium

Mitochondria are crucial players in the signaling and metabolic homeostasis of the plant cell. The molecular components that orchestrate the underlying processes, however, are largely unknown. Using a chemical biology approach, we exploited the responsiveness of Arabidopsis UDP-glucosyltransferase-encoding UGT74E2 towards mitochondrial per- turbation in order to look for novel mechanisms regulating mitochondria-to-nucleus communication. The most potent inducers of UGT74E2 shared a （2-furyl）acrylate （FAA） substructure that negatively affected mitochondrial function and was identified before as an auxin transcriptional inhibitor. Based on these premises, we demonstrated that perturbed mitochondria negatively affect the auxin signaling machinery. Moreover, chemical perturbation of polar auxin transport and auxin biosynthesis was sufficient to induce mitochondrial retrograde markers and their transcript abundance was constitutively elevated in the absence of the auxin transcriptional activators ARF7 and ARF19.

关键词： mitochondrial perturbation auxin signaling retrograde communication.

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