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Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin

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Cellular & Molecular Immunology 2020年第4期17卷 380-394页

作者： Christian Orlik Daniel Deibel Johanna Küblbeck Emre Balta Sabina Ganskih Jüri Habicht beate niesler Jutta Schröder-Braunstein Knut Schäkel Guido Wabnitz Yvonne Samstag Institute of Immunology Section Molecular ImmunologyHeidelberg UniversityIm Neuenheimer Feld 30569120 HeidelbergGermany Institute of Human Genetics Department of Human Molecular Geneticsand nCounter Core FacilityHeidelberg UniversityIm Neuenheimer Feld 36669120 HeidelbergGermany Department of Dermatology Heidelberg UniversityIm Neuenheimer Feld 44069120 HeidelbergGermany

The interplay between keratinocytes and immune cells,especially T cells,plays an important role in the pathogenesis of chronic inflammatory skin *** psoriasis,keratinocytes attract T cells by releasing chemokines,while skin-infiltrating selfreactive T cells secrete proinflammatory cytokines,e.g.,IFN γand IL-17A,that cause epidermal ***,in chronic graftversus-host disease,allogenic IFN γ-producing Th1/Tc1 and IL-17-producing Th17/Tc17 cells are recruited by keratinocyte-derived chemokines and accumulate in the ***,whether keratinocytes act as nonprofessional antigen-presenting cells to directly activate naive human T cells in the epidermis remains ***,we demonstrate that under proinflammatory conditions,primary human keratinocytes indeed activate naive human T *** activation required cell contact and costimulatory signaling via CD58/CD2 and CD54/*** T cells costimulated by keratinocytes selectively differentiated into Th1 and Th17 *** particular,keratinocyte-initiated Th1 differentiation was dependent on costimulation through CD58/*** latter molecule initiated STAT1 signaling and IFN γproduction in T *** of T cells by keratinocytes resulting in Th1 and Th17 differentiation represents a new explanation for the local enrichment of Th1 and Th17 cells in the skin of patients with a chronic inflammatory skin ***,local interference with T cell–keratinocyte interactions may represent a novel strategy for the treatment of Th1 and Th17 cell-driven skin diseases.

关键词： keratinocytes inflammatory skin diseases psoriasis human T cells costimulation CD2 LFA-1 nonprofessional antigenpresenting cells Th1 cells Th17 cells

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genetic studies in irritable bowel syndrome-status quo

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World Journal of Meta-Analysis 2018年第1期6卷 1-8页

作者： Stefan-Lucian Popa Dan L Dumitrascu Romana Vulturar beate niesler Department of 2~(nd) Medical "Iuliu Hatieganu" University of Medicine and Pharmacy Department of Cell and Molecular Biology "Iuliu Hatieganu" University of Medicine and Pharmacy Department of Human Molecular Genetics Heidelberg University

AIM To evaluate the most common studied genetic polymorphisms that may have an etiological role in irritable bowel syndrome (IBS).METHODS The data base Pub Med was searched for studies analyzing the association between gene polymorphisms and IBS. All original full papers, written in English, were retained for further analysis. The retrieved papers were further systematized according to those polymorphisms that have been detected in *** Considering these criteria, our literature search found 12 polymorphisms, residing in 10 genes, which were reported to be consistently associated with IBS. The initial search identified 189 articles, out of which 48 potentially appropriate articles were reviewed. Of these 48 articles, 41 articles were included in the review. These articles were published between 2002 and 2016. Out of these 41 studies, 17 reported analysis of the serotonin transporter (SERT) gene (SLC6A4), eight on guanine nucleotide-binding protein subunit beta-3 (GNbeta3), six on the serotonin type 3 receptor genes (HTR3A), four on (HTR3E), three on (HTR2A), three the tumor necrosis factor superfamily member TL1A gene (TNFSF15), and ten on genetic polymorphisms with limited *** Current evidence for the relation between genetic polymorphisms and IBS is limited owing to the fact that high-quality prospective studies and detailed phenotyping of patients suffering from IBS and matched controls were lacking in the past.

关键词： Irritable bowel syndrome Gene Genetic polymorphisms

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Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome:A multicenter retrospective study

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World Journal of Gastroenterology 2022年第21期28卷 2334-2349页

作者： Sabrina Berens Yuanjun Dong Nikola Fritz Jutta Walstab Mauro D'Amato Tenghao Zheng Verena Wahl Felix Boekstegers Justo Lorenzo Bermejo Cristina Martinez Stefanie Schmitteckert Egbert Clevers Felicitas Engel Annika Gauss Wolfgang Herzog Robin Spiller Miriam Goebel-Stengel Hubert Mönnikes Viola Andresen Frieling Thomas Jutta Keller Christian Pehl Christoph Stein-Thöringer Gerard Clarke Timothy G Dinan Eamonn M Quigley Gregory Sayuk Magnus Simrén Jonas Tesarz Gudrun Rappold Lukas van Oudenhove Rainer Schaefert beate niesler Department of General Internal Medicine and Psychosomatics University Hospital HeidelbergHeidelberg 69120Germany Department of Human Molecular Genetics Institute of Human GeneticsUniversity of HeidelbergHeidelberg 69120Germany Department of General Internal Medicine and Psychosomatics Internal Medicine IIUniversity Hospital HeidelbergHeidelberg 69120Germany Department of Human Molecular Genetics University of HeidelbergHeidelberg 69120Germany Gastrointestinal Genetics Lab CIC bioGUNE-BRTADerio 48160Spain IKERBASQUE Basque Foundation for ScienceBilbao 48001Spain Unit of Clinical Epidemiology Department of Medicine SolnaKarolinska InstitutetStockholm 17177Sweden Institute of Medical Biometry and Informatics Heidelberg UniversityHeidelberg 69120Germany Lleida Institute for Biomedical Research Dr.PifarréFoundation(IRBLleida) Av.Alcalde Rovira RoureLleida 25198Spain Department of Clinical and Experimental Medicine Translational Research Center for Gastrointestinal DisordersKU LeuvenLeuven 3000Belgium Department of Gastroenterology Infectious Diseases and IntoxicationsUniversity of HeidelbergHeidelberg 69120Germany Department of General Internal Medicine and Psychosomatics Heidelberg UniversityHeidelberg 69120Germany Nottingham Digestive Diseases Centre University of NottinghamNottingham NG72QLUnited Kingdom Helios Klinikum Rottweil Rottweil 78628Germany Department of Medicine Institute of Neurogastroenterology(H.M.)Martin-Luther-HospitalBelin 14193Germany Israelitisches Krankenhaus in Hamburg Hamburg 22297Germany Internal Medicine II Helios Klinikum KrefeldKrefeld 47805Germany Israelitisches Krankenhaus Hamburg Hamburg 22297Ghana Krankenhaus Vilsbiburg Vilsbiburg 84137Germany Division of Microbiome and Cancer German Cancer Research Center(DKFZ)Heidelberg 69120Germany Department of Psychiatry and Neurobehavioral Science University College CorkCork T23Ireland Medicine in Digestive Disorders Department of MedicineLynda K.and David M.Underwood Center for Digestive DisordersHou

BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with *** In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and ***,anxiety,and somatization symptoms and sociodemographic characteristics were *** functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive *** also performed separate analyses for sex and IBS *** scores were calculated as the number of minor alleles of the SNPs *** impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx *** Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in *** potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant *** We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with *** SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.

关键词： Irritable bowel syndrome 5-HT3 receptor subunit gene polymorphisms Single-nucleotide polymorphism score Depression Anxiety Somatization

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