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@ARTICLE{Breitkopf:148843,
author = {D. M. Breitkopf and V. Jankowski and K. Ohl and J. Hermann
and D. Hermert and K. Tenbrock and X. Liu and I. V. Martin
and J. Wang and F. Groll and E. Gröne$^*$ and J. Floege and
T. Ostendorf and T. Rauen and U. Raffetseder},
title = {{T}he {YB}-1:{N}otch-3 axis modulates immune cell responses
and organ damage in systemic lupus erythematosus.},
journal = {Kidney international},
volume = {97},
number = {2},
issn = {0085-2538},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2020-00035},
pages = {289-303},
year = {2020},
note = {2020 Feb;97(2):289-303},
abstract = {Systemic lupus erythematosus (SLE) is an autoimmune disease
and lupus nephritis is a major risk factor for morbidity and
mortality. Notch-3 signaling induced by membrane-bound or
soluble ligands such as YB-1 constitutes an evolutionarily
conserved pathway that determines major decisions in cell
fate. Mass spectrometry of extracellular YB-1 in sera from
patients with SLE and lupus-prone mice revealed specific
post-translational guanidinylation of two lysine residues
within the highly conserved cold-shock domain of YB-1
(YB-1-G). These modifications highly correlated with SLE
disease activity, especially in patients with lupus
nephritis and resulted in enhanced activation of Notch-3
signaling in T lymphocytes. The importance of YB-1:Notch-3
interaction in T cells was further evidenced by increased
interleukin (Il)10 expression following YB-1-G stimulation
and detection of both, YB-1-G and Notch-3, in kidneys of
MRL.lpr mice by mass spectrometry imaging. Notch-3
expression and activation was significantly up-regulated in
kidneys of 20-week-old MRL.lpr mice. Notably, lupus-prone
mice with constitutional Notch-3 depletion
(B6.Faslpr/lprNotch3-/-) exhibited an aggravated lupus
phenotype with significantly increased mortality, enlarged
lymphoid organs and aggravated nephritis. Additionally,
these mice displayed fewer regulatory T cells and reduced
amounts of anti-inflammatory IL-10. Thus, our results
indicate that the YB-1:Notch-3 axis exerts protective
effects in SLE and that Notch-3 deficiency exacerbates the
SLE phenotype.},
cin = {G130},
ddc = {610},
cid = {I:(DE-He78)G130-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31882173},
doi = {10.1016/j.kint.2019.09.031},
url = {https://inrepo02.dkfz.de/record/148843},
}