Article
The cold shock Y-box protein-1 (YB-1) promotes survival of T cells and is deregulated in Systemic Lupus Erythematosus (SLE)
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Published: | October 8, 2019 |
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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.