Journal Article

DKFZ-2020-00035

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The YB-1:Notch-3 axis modulates immune cell responses and organ damage in systemic lupus erythematosus.

Breitkopf, D. M. ; Jankowski, V. ; Ohl, K. ; Hermann, J. ; Hermert, D. ; Tenbrock, K. ; Liu, X. ; Martin, I. V. ; Wang, J. ; Groll, F. ; Gröne, E.DKFZ* ; Floege, J. ; Ostendorf, T. ; Rauen, T. ; Raffetseder, U.

2020
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.kint.2019.09.031

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.

Note: 2020 Feb;97(2):289-303

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Contributing Institute(s):

1. Zelluläre und Molekulare Pathologie (G130)

Research Program(s):

1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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