gms | German Medical Science

47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

04.09. - 07.09.2019, Dresden

The cold shock Y-box protein-1 (YB-1) promotes survival of T cells and is deregulated in Systemic Lupus Erythematosus (SLE)

Meeting Abstract

  • Stefan Meltendorf - Otto-von-Guericke Universität Magdeburg, Pädiatrie, Magdeburg
  • Hang Fu - Otto-von-Guericke Universität Magdeburg, Pädiatrie, Magdeburg
  • Mandy Pierau - Otto-von-Guericke Universität Magdeburg, Pädiatrie, Magdeburg
  • Steffi Gieseler-Halbach - Otto-von-Guericke Universität Magdeburg, Dermatologie, Magdeburg
  • Juliane Handschuh - Otto-von-Guericke Universität Magdeburg, Immunologie, Magdeburg
  • Jonathon Lindquist - Otto-von-Guericke Universität Magdeburg, Nephrologie, Magdeburg
  • Peter Mertens - Otto-von-Guericke Universität Magdeburg, Nephrologie, Magdeburg
  • Andreas Ambach - Otto-von-Guericke Universität Magdeburg, Dermatologie, Magdeburg
  • Ulrich Thomas - Leibniz-Institut für Neurobiologie Magdeburg, Neurochemie und Molekularbiologie, Magdeburg
  • Holger Lingel - Otto-von-Guericke Universität Magdeburg, Pädiatrie, Magdeburg
  • Stephanie Finzel - Department of Rheumatology and Clinical Immunology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg
  • Reinhard Voll - Department of Rheumatology and Clinical Immunology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg
  • Monika Brunner-Weinzierl - Otto-von-Guericke Universität Magdeburg, Pädiatrie, Rheumatologie, Immunologie, Magdeburg

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Dresden, 04.-07.09.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocET.35

doi: 10.3205/19dgrh154, urn:nbn:de:0183-19dgrh1543

Published: October 8, 2019

© 2019 Meltendorf et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Background: The cold-shock protein YB-1 plays a central role in cell homeostasis. Here, we analyzed the relation of YB-1 to apoptosis in primarily activated T cells from healthy donors and patients suffering from Systemic Lupus Erythematosus (SLE). We could show that YB-1 expression is hardly upregulated in apoptosis-prone T cells and in activated T cells of SLE patients. However, T cells of healthy volunteers easily induce a strong expression of YB-1.

Results: By using forced reduction of YB-1 with YB-1-shRNA we could demonstrate that failure of expression of YB-1 in activated T cells inevitably leads to caspase activation and consequently to apoptosis. In addition, we discovered that the expression of the pro-apoptotic molecule PUMA was enhanced following YB-1 knock-down. Ectopic overexpression of YB-1 revealed that survival pathways are switched on, involving enhanced protein expression of the kinase Akt and Bcl-2, even when the Fas receptor on the T cells was triggered. Chemical inactivation of Akt and PI3K indeed enhanced susceptibility to apoptosis. Thus, ectopic overexpression of YB-1 strongly promotes survival of primary T cells, even of apoptosis-prone T cells from SLE-patients.

Conclusion: Our data show failure of YB-1 upregulation in SLE patients as a yet unreported characteristic of their T cells and may refine strategies for diagnostics or even to solve their hematopoietic problems.