Bruno Kyewski

Summary

Affiliation: German Cancer Research Center
Country: Germany

Publications

  1. pmc Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels
    Jens Derbinski
    Division of Developmental Immunology, German Cancer Research Center, D 69120 Heidelberg, Germany
    J Exp Med 202:33-45. 2005
  2. pmc Medullary epithelial cells of the human thymus express a highly diverse selection of tissue-specific genes colocalized in chromosomal clusters
    Jörn Gotter
    Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany
    J Exp Med 199:155-66. 2004
  3. ncbi request reprint Promiscuous gene expression and central T-cell tolerance: more than meets the eye
    Bruno Kyewski
    Tumor Immunology Program, Division of Cellular Immunology, German Cancer Research Center, INF 280, D 69120 Heidelberg, Germany
    Trends Immunol 23:364-71. 2002
  4. ncbi request reprint How promiscuity promotes tolerance: the case of myasthenia gravis
    Bruno Kyewski
    German Cancer Research Center, Developmental Immunology, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Ann N Y Acad Sci 1132:157-62. 2008
  5. doi request reprint Immunology. A breath of Aire for the periphery
    Bruno Kyewski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, D 69120 Germany
    Science 321:776-7. 2008
  6. ncbi request reprint Aire, master of many trades
    Bruno Kyewski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, Heidelberg 69120, Germany
    Cell 140:24-6. 2010
  7. ncbi request reprint A central role for central tolerance
    Bruno Kyewski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany
    Annu Rev Immunol 24:571-606. 2006
  8. ncbi request reprint Bone marrow microenvironment facilitating dendritic cell: CD4 T cell interactions and maintenance of CD4 memory
    Markus Feuerer
    Tumor Immunology Program, German Cancer Research Center, DKFZ, D 69120 Heidelberg, Germany
    Int J Oncol 25:867-76. 2004
  9. pmc The thymic medulla: a unique microenvironment for intercellular self-antigen transfer
    Christian Koble
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany
    J Exp Med 206:1505-13. 2009
  10. pmc Epigenetic regulation of promiscuous gene expression in thymic medullary epithelial cells
    Lars Oliver Tykocinski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, D 69120 Heidelberg, Germany
    Proc Natl Acad Sci U S A 107:19426-31. 2010

Collaborators

Detail Information

Publications29

  1. pmc Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels
    Jens Derbinski
    Division of Developmental Immunology, German Cancer Research Center, D 69120 Heidelberg, Germany
    J Exp Med 202:33-45. 2005
    ..Our data document a remarkable cellular and molecular specialization of the thymic stroma in order to mimic the transcriptome of multiple peripheral tissues and, thus, maximize the scope of central self-tolerance...
  2. pmc Medullary epithelial cells of the human thymus express a highly diverse selection of tissue-specific genes colocalized in chromosomal clusters
    Jörn Gotter
    Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany
    J Exp Med 199:155-66. 2004
    ..These findings have implications for human autoimmune diseases, immuno-therapy of tumors, and the understanding of the nature of this unorthodox regulation of gene expression...
  3. ncbi request reprint Promiscuous gene expression and central T-cell tolerance: more than meets the eye
    Bruno Kyewski
    Tumor Immunology Program, Division of Cellular Immunology, German Cancer Research Center, INF 280, D 69120 Heidelberg, Germany
    Trends Immunol 23:364-71. 2002
  4. ncbi request reprint How promiscuity promotes tolerance: the case of myasthenia gravis
    Bruno Kyewski
    German Cancer Research Center, Developmental Immunology, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Ann N Y Acad Sci 1132:157-62. 2008
    ....
  5. doi request reprint Immunology. A breath of Aire for the periphery
    Bruno Kyewski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, D 69120 Germany
    Science 321:776-7. 2008
  6. ncbi request reprint Aire, master of many trades
    Bruno Kyewski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, Heidelberg 69120, Germany
    Cell 140:24-6. 2010
    ..By analyzing Aire's interacting partners, Abramson et al. (2010) shed new light on this unorthodox form of gene expression...
  7. ncbi request reprint A central role for central tolerance
    Bruno Kyewski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany
    Annu Rev Immunol 24:571-606. 2006
    ....
  8. ncbi request reprint Bone marrow microenvironment facilitating dendritic cell: CD4 T cell interactions and maintenance of CD4 memory
    Markus Feuerer
    Tumor Immunology Program, German Cancer Research Center, DKFZ, D 69120 Heidelberg, Germany
    Int J Oncol 25:867-76. 2004
    ..Together these findings suggest that DC-T cell interactions in BM play an important role in immune responses to blood-borne antigen and in the establishment of systemic immunity and long-term memory...
  9. pmc The thymic medulla: a unique microenvironment for intercellular self-antigen transfer
    Christian Koble
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany
    J Exp Med 206:1505-13. 2009
    ....
  10. pmc Epigenetic regulation of promiscuous gene expression in thymic medullary epithelial cells
    Lars Oliver Tykocinski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, D 69120 Heidelberg, Germany
    Proc Natl Acad Sci U S A 107:19426-31. 2010
    ..Transient gene expression could conceivably add to the local diversity of self-antigen display thus enhancing the efficacy of central tolerance...
  11. pmc Overlapping gene coexpression patterns in human medullary thymic epithelial cells generate self-antigen diversity
    Sheena Pinto
    Division of Developmental Immunology, German Cancer Research Center DKFZ, 69120 Heidelberg, Germany
    Proc Natl Acad Sci U S A 110:E3497-505. 2013
    ..These findings have implications for the temporal and spatial (re)presentation of self-antigens in the medulla in the context of tolerance induction. ..
  12. ncbi request reprint Promiscuous gene expression and the developmental dynamics of medullary thymic epithelial cells
    Jana Gäbler
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany
    Eur J Immunol 37:3363-72. 2007
    ..Our data document that mTEC represent a highly dynamic cell population, and they imply that the availability and display of TRA in the thymus undergoes a perpetual temporal and spatial reorganization...
  13. doi request reprint An organotypic coculture model supporting proliferation and differentiation of medullary thymic epithelial cells and promiscuous gene expression
    Sheena Pinto
    Division of Developmental Immunology, German Cancer Research Center, 69120 Heidelberg, Germany
    J Immunol 190:1085-93. 2013
    ..This in vitro culture model should facilitate the identification of molecular components and pathways involved in mTEC differentiation in general and in promiscuous gene expression in particular...
  14. ncbi request reprint CREB function is required for normal thymic cellularity and post-irradiation recovery
    Sven Baumann
    Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Eur J Immunol 34:1961-71. 2004
    ..These data show that loss of CREB function has specific effects on thymic T lymphocyte proliferation and homeostasis in vivo...
  15. pmc Promiscuous gene expression patterns in single medullary thymic epithelial cells argue for a stochastic mechanism
    Jens Derbinski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany
    Proc Natl Acad Sci U S A 105:657-62. 2008
    ....
  16. pmc An evolutionarily conserved mutual interdependence between Aire and microRNAs in promiscuous gene expression
    Olga Ucar
    Division of Developmental Immunology, German Cancer Research Center, Heidelberg, Germany
    Eur J Immunol 43:1769-78. 2013
    ..In contrast, the absence of miR-29a only affected the Aire-dependent gene pool. These findings reveal a mutual interdependence of miRNA and Aire. ..
  17. ncbi request reprint Regulating self-tolerance by deregulating gene expression
    Jörn Gotter
    Tumour Immunology Program, Division of Developmental Immunology, German Cancer Research Centre DKFZ, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Curr Opin Immunol 16:741-5. 2004
    ..The identification of the molecular components controlling the expression of tissue-restricted genes in the thymus promises to add valuable new insights into the complex genetic regulation underlying most autoimmune diseases...
  18. ncbi request reprint Self-representation in the thymus: an extended view
    Bruno Kyewski
    Tumour Immunology Programme, Division of Developmental Immunology, German Cancer Research Centre, Im Neuenheimer Feld 280, D 69120, Heidelberg, Germany
    Nat Rev Immunol 4:688-98. 2004
    ..As we discuss here, these new insights have implications for our understanding of self-tolerance in humans, its breakdown in autoimmune diseases and the significance of this tolerance mode in vertebrate evolution...
  19. doi request reprint How thymic antigen presenting cells sample the body's self-antigens
    Jens Derbinski
    Department of Developmental Immunology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    Curr Opin Immunol 22:592-600. 2010
    ..The combinatorial expression patterns of these attributes in distinct APC subsets result in a self-peptide display partly unique to the cortex mediating positive selection and to the medulla mediating tolerance induction...
  20. ncbi request reprint Linking signalling pathways, thymic stroma integrity and autoimmunity
    Jens Derbinski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Trends Immunol 26:503-6. 2005
    ..In a recent study, tumour necrosis factor receptor-associated factor 6 (TRAF6) has been identified as an essential component of a new signalling pathway directing mTEC development...
  21. ncbi request reprint Highly variable expression of tissue-restricted self-antigens in human thymus: implications for self-tolerance and autoimmunity
    Richard Taubert
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany
    Eur J Immunol 37:838-48. 2007
    ..The considerable, yet selective variability in thymic expression levels of target auto-antigen expression might constitute a hitherto underestimated risk factor for the susceptibility of autoimmune diseases in man...
  22. ncbi request reprint The thymus medulla slowly yields its secrets
    Lars Oliver Tykocinski
    Division of Developmental Immunology, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany
    Ann N Y Acad Sci 1143:105-22. 2008
    ..Furthermore, we emphasize the importance of promiscuous expression of particular tissue-restricted self-antigens in preventing organ-specific autoimmunity and evaluate new data supporting the threshold model of central tolerance...
  23. pmc Dynamic changes during the immune response in T cell-antigen-presenting cell clusters isolated from lymph nodes
    Mirja Hommel
    Tumor Immunology Program, Division of Cellular Immunology, German Cancer Research Center DKFZ, D 69120 Heidelberg, Germany
    J Exp Med 197:269-80. 2003
    ..The results provide a basis for the analysis of short range, mutual cell-cell interactions within such confined microenvironments...
  24. ncbi request reprint Bone marrow as a priming site for T-cell responses to blood-borne antigen
    Markus Feuerer
    Tumor Immunology Program, German Cancer Research Center DKFZ, Heidelberg, Germany
    Nat Med 9:1151-7. 2003
    ..These findings highlight the uniqueness of bone marrow as an organ important for hemato- and lymphopoiesis and for systemic T cell-mediated immunity...
  25. ncbi request reprint An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus
    Matthieu Giraud
    INSERM, U580, 75015 Paris, France
    Nature 448:934-7. 2007
    ....
  26. ncbi request reprint Expression of tumor-associated differentiation antigens, MUC1 glycoforms and CEA, in human thymic epithelial cells: implications for self-tolerance and tumor therapy
    Silvie Cloosen
    Division of Hematology, Department of Internal Medicine, Growth and Development Research Institute, University Hospital Maastricht, The Netherlands
    Cancer Res 67:3919-26. 2007
    ..Knowledge of these subtleties in promiscuous gene expression may, in the future, assist the selection of T cell tumor vaccines for clinical trials...
  27. ncbi request reprint Expression of a natural tumor antigen by thymic epithelial cells impairs the tumor-protective CD4+ T-cell repertoire
    Rinke Bos
    Department of Immunohematology and Blood Transfusion, Tumor Immunology Group, Leiden University Medical Center, Leiden, Netherlands
    Cancer Res 65:6443-9. 2005
    ....
  28. ncbi request reprint Expression profiling of autoimmune regulator AIRE mRNA in a comprehensive set of human normal and neoplastic tissues
    Thorsten Klamp
    Department of Internal Medicine III, Johannes Gutenberg University Mainz, Obere Zahlbacherstr 63, 55131 Mainz, Germany
    Immunol Lett 106:172-9. 2006
    ..On this broad data basis we found that AIRE mRNA expression is confined to mTECs in thymus and to lymph node tissue and that DNA hypomethylation contributes to transcriptional control of this gene...
  29. pmc Foxp3+ CD25+ regulatory T cells specific for a neo-self-antigen develop at the double-positive thymic stage
    Julie Cabarrocas
    Institut National de la Sante et de la Recherche Medicale U563, Purpan Hospital, 31000 Toulouse, France
    Proc Natl Acad Sci U S A 103:8453-8. 2006
    ..Our data show that the promiscuous expression of the HA transgene in thymic epithelial cells is involved in the selective induction and/or expansion of HA-specific Foxp3(+) Treg thymic precursors as early as the double-positive stage...