The cold shock protein YB-1 (Y-box protein-1) in chronic T cell responses and systemic lupus erythematosus (SLE)
Final Report Abstract
Understanding how deregulated apoptosis - not only of SLE T-cells - can be manipulated is a fundamental question in immunology. Within the project we could demonstrate for the first time that SLE T-cells can hardly upregulate the cold shock protein YB-1. Expression was a prerequisite for survival and has directed us to generate a model that explains chronicity of the SLE pathology. We identified PUMA for induction of apoptosis in the absence of YB-1 and the kinase Akt to be responsible for YB-1 mediated resistance against activation induced cell death. The results demonstrate that reduced YB-1 accumulation is a novel signatory function of SLE T-cells. Our results stress also the point that SLE cells show viability when YB-1 is re-expressed and, thus, can be manipulated by impinging on YB-1 signal transduction.
Publications
- Inflammatory cell infiltration and resolution of kidney inflammation is orchestrated by the cold-shock protein Y-box binding protein-1. Kidney Int. 2017;92(5):1157-1177
Bernhardt A, Fehr A, Brandt S, Jerchel S, Ballhause TM, Philipsen L, Stolze S, Geffers R, Weng H, Fischer KD, Isermann B, Brunner-Weinzierl MC, Batra A, Siegmund B, Zhu C, Lindquist JA, Mertens PR
(See online at https://doi.org/10.1016/j.kint.2017.03.035) - RSK-mediated nuclear accumulation of the cold-shock Y-box protein-1 controls proliferation of T cells and T-ALL blasts. . Cell Death Differ. 2017;24(2):371-383
Gieseler-Halbach S, Meltendorf S, Pierau M, Weinert S, Heidel FH, Fischer T, Handschuh J, Braun-Dullaeus RC, Schrappe M, Lindquist JA, Mertens PR, Thomas U, Brunner-Weinzierl MC
(See online at https://doi.org/10.1038/cdd.2016.141) - Failure of upregulation of the cold shock Y-box protein-1 in effector T-cells of systemic lupus erythematosus patients averts cell survival. Arthritis & Rheumatol. 2020
Meltendorf S, Fu H, Pierau M, Lindquist JA, Finzel S, Mertens PR, Gieseler-Halbach S, Ambach A, Thomas U, Lingel H, Voll RE, Brunner-Weinzierl MC
(See online at https://doi.org/10.1002/art.41382)
