Research Topics
Genomes and Genes
| Walter ReithSummaryAffiliation: University of Geneva Country: Switzerland Publications
| Collaborators
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Detail Information
Publications
Maturation of dendritic cells is accompanied by rapid transcriptional silencing of class II transactivator (CIITA) expressionS Landmann
Department of Genetics and Microbiology, University of Geneva Medical School, CMU, 1211 Geneva, Switzerland
J Exp Med 194:379-91. 2001..This is mediated by a global repression mechanism implicating histone deacetylation over a large domain spanning the entire MHC2TA regulatory region...- Selective abrogation of major histocompatibility complex class II expression on extrahematopoietic cells in mice lacking promoter IV of the class II transactivator geneJ M Waldburger
Department of Genetics and Microbiology, University of Geneva Medical School, 1211 Geneva 4, Switzerland
J Exp Med 194:393-406. 2001..Moreover, they represent a unique animal model for studying the significance and contribution of MHCII-mediated antigen presentation by nonprofessional antigen-presenting cells in health and disease... 
Regulation of MHC class II gene expression by the class II transactivatorWalter Reith
Department of Pathology and Immunology, University of Geneva Medical School, Centre Medical Universitaire, 1 rue Michel Servet, CH 1211, Geneva, Switzerland
Nat Rev Immunol 5:793-806. 2005....- The bare lymphocyte syndrome and the regulation of MHC expressionW Reith
Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, 1 rue Michel Servet, Geneva 4, 1211 Switzerland
Annu Rev Immunol 19:331-73. 2001..The study of RFX and CIITA has made major contributions to our comprehension of the molecular mechanisms controlling MHCII genes and has made this system into a textbook model for the regulation of gene expression... - The transcription factor Rfx3 regulates beta-cell differentiation, function, and glucokinase expressionAouatef Ait-Lounis
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Centre Medical Universitaire, Geneva, Switzerland
Diabetes 59:1674-85. 2010..The objective of this work was to unravel the cellular and molecular mechanisms underlying this deficiency... - Identification of CIITA regulated genetic module dedicated for antigen presentationMichal Krawczyk
University of Geneva Medical School, CMU, Geneva, Switzerland
PLoS Genet 4:e1000058. 2008.... - Long distance control of MHC class II expression by multiple distal enhancers regulated by regulatory factor X complex and CIITAMichal Krawczyk
University of Geneva Medical School, Centre Medical Universitaire, 1 rue Michel Servet, CH 1211 Geneva, Switzerland
J Immunol 173:6200-10. 2004..These results reveal a hitherto unexpected level of complexity involving long distance control of MHC-II expression by multiple distal regulatory elements... - MHC class II-restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell-mediated autoimmunityMagali Irla
Department of Pathology, University of Geneva Medical School, 1211 Geneva, Switzerland
J Exp Med 207:1891-905. 2010..pDCs thus function as APCs during the course of EAE and confer a natural protection against autoimmune disease development that is mediated directly by their ability to present of Ags to CD4(+) T cells in vivo... - New functions of the major histocompatibility complex class II-specific transcription factor RFXANK revealed by a high-resolution mutagenesis studyMichal Krawczyk
Department of Pathology and Immunology, University of Geneva Medical School, CMU, 1 rue Michel Servet, CH 1211 Geneva, Switzerland
Mol Cell Biol 25:8607-18. 2005.... - MHC class II expression is differentially regulated in plasmacytoid and conventional dendritic cellsSalome Leibundgut-Landmann
Department of Pathology and Immunology, University of Geneva Medical School, 1211 Geneva, Switzerland
Nat Immunol 5:899-908. 2004..The molecular mechanisms driving MHC class II expression in pDCs are thus akin to those operating in lymphoid rather than myeloid cells... - Transcription-coupled deposition of histone modifications during MHC class II gene activationNatalia Rybtsova
Department of Pathology and Immunology, University of Geneva Medical School, 1 rue Michel Servet, CH 1211, Geneva, Switzerland
Nucleic Acids Res 35:3431-41. 2007..These results provide strong evidence that transcription elongation can play a decisive role in the deposition of histone modification patterns associated with inducible gene activation... - Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genesSalome Leibundgut-Landmann
Department of Pathology, University of Geneva Medical School, Geneva, Switzerland
Eur J Immunol 34:1513-25. 2004.... - Revisiting the specificity of the MHC class II transactivator CIITA in vivoLuc A Otten
Department of Pathology and Immunology, University of Geneva Medical School, Switzerland
Eur J Immunol 36:1548-58. 2006..They also imply that precisely regulated MHC-II expression is essential for maintaining a proper Th1-Th2 balance... 
Cx36 is a target of Beta2/NeuroD1, which associates with prenatal differentiation of insulin-producing β cellsRachel Nlend Nlend
Department of Cell Physiology and Metabolism, University of Geneva, CMU, 1 rue Michel Servet CH 1211, Geneva 4, Switzerland
J Membr Biol 245:263-73. 2012..The data identify Cx36 as a novel early marker of β cells and as a target of Beta2/NeuroD1, which is essential for β-cell development and differentiation...- The transcription factor RFX protects MHC class II genes against epigenetic silencing by DNA methylationQueralt Seguín-Estévez
Faculty of Medicine, University of Geneva, Geneva, Switzerland
J Immunol 183:2545-53. 2009..This function is likely to be crucial for retaining MHCII genes in an open chromatin configuration permissive for activation in MHCII-negative cells, such as the precursors of APC and nonprofessional APC before induction with IFN-gamma... - Expression of RAB4B, a protein governing endocytic recycling, is co-regulated with MHC class II genesMichal Krawczyk
Department of Pathology and Immunology, University of Geneva Medical School, CMU, 1 rue Michel Servet, CH 1211 Geneva, Switzerland
Nucleic Acids Res 35:595-605. 2007..This molecular link between the transcriptional activation of RAB4B and MHC class II genes implies that APC boost their antigen presentation capacity by increasing RAB4-mediated endocytic recycling... - Chromatin remodeling and extragenic transcription at the MHC class II locus control regionKrzysztof Masternak
University of Geneva Medical School, CMU, Switzerland
Nat Immunol 4:132-7. 2003..The finding that RFX and CIITA regulate the function of the MHC class II LCR reveals an unexpected degree of complexity in the mechanisms controlling MHC class II gene expression... - Nucleosome eviction from MHC class II promoters controls positioning of the transcription start siteElisa Leimgruber
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, CH 1211, Geneva, Switzerland
Nucleic Acids Res 37:2514-28. 2009..Our results provide support for a novel mechanism in transcription initiation whereby the position of the TSS is controlled by nucleosome eviction rather than by promoter sequence... - Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and functionIsabelle Dunand-Sauthier
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Blood 117:4490-500. 2011..These results indicate that silencing of c-Fos expression by miR155 is a conserved process that is required for DC maturation and function... - The S box of major histocompatibility complex class II promoters is a key determinant for recruitment of the transcriptional co-activator CIITAAnnick Muhlethaler-Mottet
University of Geneva Medical School, Department of Pathology and Immunology, , 1 rue Michel-Servet, CH-1211, Geneva, Switzerland
J Biol Chem 279:40529-35. 2004..This paves the way for the identification of novel factors mediating the contribution of the S box to the activation of MHC class II promoters... - RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiencyB Durand
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland
EMBO J 16:1045-55. 1997..Complementation of the 6.1.6 and DA cell lines by transfection with RFXAP fully restores expression of all endogenous MHC-II genes in vivo, demonstrating that RFXAP is a novel essential MHC-II regulatory gene... - Mutation of RFXAP, a regulator of MHC class II genes, in primary MHC class II deficiencyJ Villard
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland
N Engl J Med 337:748-53. 1997..There are three known complementation groups (A, B, and C)... - A novel DNA-binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome)V Steimle
Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland
Genes Dev 9:1021-32. 1995..Mutations in the RFX5 gene have been characterized in two patients. Transfection of the patient's cells with the RFX5 cDNA repairs the binding defect and fully restores expression of all the endogenous MHC class II genes in vivo... - Three-dimensional visualization of the mouse thymus organization in health and immunodeficiencyMagali Irla
Department of Pathology and Immunology, University of Geneva, 1211 Geneva, Switzerland
J Immunol 190:586-96. 2013.... - Direct genetic correction as a new method for diagnosis and molecular characterization of MHC class II deficiencyFranck Matheux
Department of Genetics and Microbiology, University of Geneva Medical School, Geneva, Switzerland
Mol Ther 6:824-9. 2002..Molecular analysis confirmed the presence of homozygous mutations in the RFXANK and RFXAP genes, respectively. Direct genetic correction represents a valuable tool for the diagnosis and classification of new MHCII-deficiency patients... - A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patientsK Masternak
Louis Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland
Nat Genet 20:273-7. 1998..RFXANK contains a protein-protein interaction region consisting of three ankyrin repeats. Its interaction with RFX5 and RFXAP is essential for binding of the RFX complex to MHC-II promoters... - Novel function of the ciliogenic transcription factor RFX3 in development of the endocrine pancreasAouatef Ait-Lounis
Department of Pathology and Immunology, University of Geneva Medical School, 1 rue Michel Servet, CH 1211, Geneva, Switzerland
Diabetes 56:950-9. 2007..These findings suggest that RFX3 participates in the mechanisms that govern pancreatic endocrine cell differentiation and that the presence of primary cilia on islet cells may play a key role in this process... - Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularityMagali Irla
University of Geneva Medical School, CMU, 1 rue Michel Servet, CH 1211, Geneva, Switzerland
Immunity 29:451-63. 2008.... - Promoter-specific functions of CIITA and the MHC class II enhanceosome in transcriptional activationKrzysztof Masternak
Department of Genetics and Microbiology, University of Geneva Medical School, 1 rue Michel-Servet, , Switzerland
EMBO J 21:1379-88. 2002..Our results support the general notion that the impact of a particular activator on transcription in vivo may vary depending on the promoter and the chromatin context... - Analysis of mutations and chromosomal localisation of the gene encoding RFX5, a novel transcription factor affected in major histocompatibility complex class II deficiencyJ Villard
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland
Hum Mutat 10:430-5. 1997.... - RFX1, a transactivator of hepatitis B virus enhancer I, belongs to a novel family of homodimeric and heterodimeric DNA-binding proteinsW Reith
Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Centre Medical Universitaire, Switzerland
Mol Cell Biol 14:1230-44. 1994..RFX proteins share several novel features, including new DNA-binding and dimerization motifs and a peculiar dependence on methylated CpG dinucleotides at certain sites... - Autoimmunity and inflammation are independent of class II transactivator type PIV-dependent class II major histocompatibility complex expression in peripheral tissues during collagen-induced arthritisJean Marc Waldburger
University Medical Center and University of Geneva, Geneva, Switzerland
Arthritis Rheum 63:3354-63. 2011.... - Control of central self-tolerance induction by autoreactive CD4+ thymocytesMagali Irla
University of Geneva, Faculty of Medicine, CMU, 1 rue Michel Servet, CH 1211, Geneva, Switzerland
Trends Immunol 31:71-9. 2010.... - Critical role of TLR7 in the acceleration of systemic lupus erythematosus in TLR9-deficient miceMarie Laure Santiago-Raber
Department of Pathology and Immunology, University of Geneva, 1 rue Michel Servet, 1211 Geneva 4, Switzerland
J Autoimmun 34:339-48. 2010.... - The DNA-binding defect observed in major histocompatibility complex class II regulatory mutants concerns only one member of a family of complexes binding to the X boxes of class II promotersC Herrero Sanchez
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland
Mol Cell Biol 12:4076-83. 1992..This report also illustrates the need for caution in correlating specific cloned proteins with nuclear factors identified by DNA-binding assays, particularly when dealing with families of related proteins... - Function of major histocompatibility complex class II promoters requires cooperative binding between factors RFX and NF-YW Reith
Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland
Proc Natl Acad Sci U S A 91:554-8. 1994.... - Regulation of MHC class II expression, a unique regulatory system identified by the study of a primary immunodeficiency diseaseM Krawczyk
University of Geneva Medical School, CMU, Switzerland
Tissue Antigens 67:183-97. 2006..The function of CIITA in transcriptional regulation of MHC-II genes could thus be a recent acquisition by an ancestral protein having a role in an unrelated system... - Regulation of MHC class II genes: lessons from a diseaseB Mach
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland
Annu Rev Immunol 14:301-31. 1996..Finally, the facts that CIITA and RFX5 are both essential and highly specific for MHC-II genes make possible novel strategies designed to achieve immunomodulation via transcriptional intervention... - A functionally essential domain of RFX5 mediates activation of major histocompatibility complex class II promoters by promoting cooperative binding between RFX and NF-YJ Villard
Department of Genetics and Microbiology, University of Geneva Medical School, CH 1211 Geneva 4, Switzerland
Mol Cell Biol 20:3364-76. 2000..This provides direct evidence that RFX5-mediated cooperative binding between RFX and NF-Y plays an essential role in the transcriptional activation of MHC-II genes... - Deletion of glutamate dehydrogenase in beta-cells abolishes part of the insulin secretory response not required for glucose homeostasisStefania Carobbio
Department of Cell Physiology and Metabolism, Geneva, Switzerland
J Biol Chem 284:921-9. 2009..The results demonstrate that GDH is essential for the full development of the secretory response in beta-cells. However, maximal secretory capacity is not required for maintenance of glucose homeostasis in normo-caloric conditions... - Pancreatic inactivation of c-Myc decreases acinar mass and transdifferentiates acinar cells into adipocytes in miceClaire Bonal
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
Gastroenterology 136:309-319.e9. 2009..The basic helix-loop-helix transcription factor c-Myc is one of the main regulators of these processes in many organs. We studied the requirement of c-Myc in controlling the generation and maintenance of pancreatic mass... - The genes for MHC class II regulatory factors RFX1 and RFX2 are located on the short arm of chromosome 19L Pugliatti
Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland
Genomics 13:1307-10. 1992..1 and RFX2 at 19p13.2-p13.3. These two regulatory genes are thus assigned to a region of high gene density and RFX1 is close to another DNA-binding factor, LYL1... - The different level of expression of HLA-DRB1 and -DRB3 genes is controlled by conserved isotypic differences in promoter sequenceP Emery
Department of Genetics and Microbiology, University of Geneva Medical School, Geneva, Switzerland
Hum Immunol 38:137-47. 1993..Finally, analysis of the activity of various normal and mutated DRB1 or DRB3 promoters indicates that the X box region of these promoters plays a dominant role in controlling the relative levels of HLA-DRB1 and -DRB3 gene expression... - Expression of the three human major histocompatibility complex class II isotypes exhibits a differential dependence on the transcription factor RFXAPM Peretti
Department of Genetics and Microbiology, University of Geneva Medical School, CMU, 1 rue Michel Servet, 1211 Geneva, Switzerland
Mol Cell Biol 21:5699-709. 2001..Expression of the three MHCII isotypes exhibits a differential requirement for this domain. We show that this is due to a differential dependence on this domain for promoter occupation and recruitment of the coactivator CIITA in vivo... - MHC class II regulatory factor RFX has a novel DNA-binding domain and a functionally independent dimerization domainW Reith
Department of Microbiology, University of Geneva Medical School, Switzerland
Genes Dev 4:1528-40. 1990..It also implies that an RFX homodimer has two potential DNA-binding sites. We therefore speculate that RFX could form a DNA loop by cross-linking the two X-box sequences found far apart upstream of MHC class II genes... - RFX proteins, a novel family of DNA binding proteins conserved in the eukaryotic kingdomP Emery
Department of Genetics and Microbiology, University of Geneva Medical School, Centre Medical Universtaire, Switzerland
Nucleic Acids Res 24:803-7. 1996.... - RFX1 is identical to enhancer factor C and functions as a transactivator of the hepatitis B virus enhancerC A Siegrist
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland
Mol Cell Biol 13:6375-84. 1993..Interestingly, transactivation of EnhI by RFX1 (EF-C) is not observed in cell lines that are not of liver origin, suggesting that the ubiquitous RFX1 protein cooperates with liver-specific factors... - Antigen recognition by autoreactive CD4⁺ thymocytes drives homeostasis of the thymic medullaMagali Irla
Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland
PLoS ONE 7:e52591. 2012..Our results show that Ag-dependent interactions between autoreactive CD4⁺ thymocytes and mTECs fine-tune homeostasis of the medulla by completing the signaling axes implicated in mTEC expansion and medullary organization... - Proteasome blockade exerts an antifibrotic activity by coordinately down-regulating type I collagen and tissue inhibitor of metalloproteinase-1 and up-regulating metalloproteinase-1 production in human dermal fibroblastsSerena Fineschi
Immunology and Allergy, Department of Internal Medicine, Geneva University Hospital, Geneva School of Medicine, Geneva, Switzerland
FASEB J 20:562-4. 2006..Thus, the coordinated down-regulation of collagen and TIMP-1 and up-regulation of MMP-1 renders proteasome blockade an attractive strategy for treating conditions as SSc, characterized by excessive fibrosis... - Promoter IV of the class II transactivator gene is essential for positive selection of CD4+ T cellsJean Marc Waldburger
Institute of Biochemistry and Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland
Blood 101:3550-9. 2003..We found that the Jak/STAT pathways activated by the common gamma chain (CD132) or common beta chain (CDw131) cytokine receptors are not required for MHCII expression in thymic cortical epithelia... - New dimensions of CIITAWalter Reith
Nat Immunol 9:713-4. 2008 - RFX1 and NF-1 associate with P sequences of the human growth hormone locus in pituitary chromatinLisa D Norquay
Department of Physiology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada R3E 3J7
Mol Endocrinol 17:1027-38. 2003..Taken together, our data suggest that an inverse relationship exists between 263P and CS promoter histone hyperacetylation and the association of these factors in vivo... - ComPLEXIN new targets for CIITAWalter Reith
Nat Immunol 4:819-20. 2003 - In vivo, RFX5 binds differently to the human leucocyte antigen-E, -F, and -G gene promoters and participates in HLA class I protein expression in a cell type-dependent mannerPhilippe Rousseau
CEA, , DSV/DRM, , , Paris, France
Immunology 111:53-65. 2004..RFX5 and CIITA are thus not involved in HLA-G expression and their importance for the surface expression of HLA-E/classical HLA class I molecules may vary depending on the cell type... - Deregulated MHC class II transactivator expression leads to a strong Th2 bias in CD4+ T lymphocytesLuc A Otten
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland
J Immunol 170:1150-7. 2003..These results imply that CIITA is not a direct Th1-specific repressor of the IL-4 gene and that tight control over the expression of CIITA and MHC-II is required to maintain the normal balance between Th1 and Th2 responses... - The brain as an immune privileged site: dendritic cells of the central nervous system inhibit T cell activationTobias Suter
Section of Clinical Immunology, University Hospital, , Switzerland
Eur J Immunol 33:2998-3006. 2003..TGFbeta, IL-10 and TRAIL were found to significantly contribute to the CNS-DC-mediated inhibition of allo-T cell proliferation. Thus CNS-DC may be the key responsibles for maintaining immune privilege within the inflamed CNS... - TGFbeta directs gene expression of activated microglia to an anti-inflammatory phenotype strongly focusing on chemokine genes and cell migratory genesRey Paglinawan
Section of Clinical Immunology, Department of Internal Medicine, , , Switzerland
Glia 44:219-31. 2003..Taken collectively, the data strongly suggest that one of the main effects of TGFbeta is to impair cell entry into the CNS and to hinder migration of microglia in the CNS parenchyma... - TGFbeta receptor II gene deletion in leucocytes prevents cerebral vasculitis in bacterial meningitisUrsula Malipiero
Clinical Immunology, University Hospital Zurich, Zurich, Switzerland
Brain 129:2404-15. 2006..L-selectin is known to be essential for PMN recruitment in bacterial meningitis. We conclude that defective TGFbeta signalling in PMN is beneficial in bacterial meningitis by ameliorating migration of PMN and bacterial clearance... - Functional CD8+ but not CD4+ T cell responses develop independent of thymic epithelial MHCMarianne M Martinic
Institute of Experimental Immunology, University Hospital Zurich, CH 8091 Zurich, Switzerland
Proc Natl Acad Sci U S A 103:14435-40. 2006..Thus, maturation of functional CD4+ T cell responses required MHC class II on thymic epithelium, whereas CD8+ T cells matured in the absence of TE MHC... - Circulating, soluble forms of major histocompatibility complex antigens are not exosome-associatedPhilippa A MacKay
Department of Microbiology and Immunology, Dunedin, New Zealand
Eur J Immunol 36:2875-84. 2006..This suggests that myeloid dendritic cells and/or macrophages, which preferentially use promoter pI of the C2ta gene, produce most of the sMHC class II found in the circulation...