Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/85913
Title: Cell survival failure in effector T cells from patients with systemic lupus erythematosus following insufficient up‐regulation of cold‐shock Y‐box binding protein 1
Author(s): Meltendorf, Stefan
Fu, Hang
Pierau, MandyLook up in the Integrated Authority File of the German National Library
Lindquist, Jonathan A.
Finzel, StephanieLook up in the Integrated Authority File of the German National Library
Mertens, Peter ReneLook up in the Integrated Authority File of the German National Library
Gieseler-Halbach, Steffi
Ambach, AndreasLook up in the Integrated Authority File of the German National Library
Thomas, Ulrich
Lingel, HolgerLook up in the Integrated Authority File of the German National Library
Voll, ReinhardLook up in the Integrated Authority File of the German National Library
Brunner-Weinzierl, MonikaLook up in the Integrated Authority File of the German National Library
Issue Date: 2020
Type: Article
Language: English
URN: urn:nbn:de:gbv:ma9:1-1981185920-878663
Subjects: T-cells
Systemic Lupus Erythematosus
Cold-Shock Y-Box Binding Protein 1
Abstract: Objective. The importance of cold-shock Y-box binding protein 1 (YB-1) for cell homeostasis is well-documented based on prior observations of its association with certain cancer entities. This study was undertaken to explore the role of YB-1 in T cell homeostasis and survival and the potential contribution of YB-1 to the pathogenesis of systemic lupus erythematosus (SLE). Methods. In the peripheral blood from 25 SLE patients and 25 healthy donors, the expression of YB-1 and frequency of T cell apoptosis was analyzed by quantitative polymerase chain reaction (qPCR) and fluorescenceactivated cell sorting of CD4+ T cells ex vivo and also analyzed in T cells in vitro after 6 days of stimulation with anti- CD3–coupled or anti-CD3/anti-CD28–coupled microspheres. YB-1 was overexpressed using lentiviral transduction with wild-type green fluorescent protein (wtGFP) YB-1, and knockdown of YB-1 was achieved using specific short hairpin RNA (shRNA) (3-fold reduction; P < 0.0001). Results. YB-1 expression was significantly lower in apoptosis-prone T cells and in activated T cells from SLE patients compared to YB-1 expression in nonapoptotic T cells and activated T cells from healthy donors (P = 0.001). Knockdown of YB-1 in T cells consequently led to expression of proapoptotic molecules and caspase 3 activation (1.6-fold), and subsequently, to apoptosis. Furthermore, YB-1 promoted survival pathways involving enhanced protein expression of the kinase Akt (2-fold) and Bcl-2 (3-fold), even when Fas/CD95 was triggered. YB-1–mediated T cell survival was reversed by Akt and phosphatidylinositol 3-kinase (PI3K) inactivation. In SLE patients, rescue of YB-1 expression strongly promoted survival of T cells and even prevented cell death in T cells that were extremely apoptosis-prone. Conclusion. Our data show that failure of YB-1 up-regulation in T cells from SLE patients led to enhanced apoptosis. These findings imply that YB-1 plays a crucial role in the disturbed homeostasis of activated T cells leading to hematopoietic alterations in SLE. These insights may help facilitate the development of new treatment strategies for SLE.
URI: https://opendata.uni-halle.de//handle/1981185920/87866
http://dx.doi.org/10.25673/85913
Open Access: Open access publication
License: (CC BY-NC 4.0) Creative Commons Attribution NonCommercial 4.0(CC BY-NC 4.0) Creative Commons Attribution NonCommercial 4.0
Sponsor/Funder: Projekt DEAL 2020
Journal Title: Arthritis & rheumatology
Publisher: Wiley
Publisher Place: Hoboken, NJ
Volume: 72
Issue: 10
Original Publication: 10.1002/art.41382
Page Start: 1721
Page End: 1733
Appears in Collections:Medizinische Fakultät (OA)

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