The lymphotoxin β receptor is a potential therapeutic target in renal inflammation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-01

AUTHORS

Gitta Seleznik, Harald Seeger, Judith Bauer, Kai Fu, Julie Czerkowicz, Adrian Papandile, Uriana Poreci, Dania Rabah, Ann Ranger, Clemens D Cohen, Maja Lindenmeyer, Jin Chen, Ilka Edenhofer, Hans J Anders, Maciej Lech, Rudolf P Wüthrich, Nancy H Ruddle, Marcus J Moeller, Nicolas Kozakowski, Heinz Regele, Jeffrey L Browning, Mathias Heikenwalder, Stephan Segerer

ABSTRACT

Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin β receptor (LTβR) signaling is crucial for the formation of lymphoid tissue, and inhibition of LTβR signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LTβR signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LTα and LTβ ligands, as well as LTβR. The LTβR protein and mRNA were localized to tubular epithelial cells, parietal epithelial cells, crescents, and cells of the glomerular tuft, whereas LTβ was found on lymphocytes and tubular epithelial cells. Human tubular epithelial cells, mesangial cells, and mouse parietal epithelial cells expressed both LTα and LTβ mRNA upon stimulation with TNF in vitro. Several chemokine mRNAs and proteins were expressed in response to LTβR signaling. Importantly, in a murine lupus model, LTβR blockade improved renal function without the reduction of serum autoantibody titers or glomerular immune complex deposition. Thus, a preclinical mouse model and human studies strongly suggest that LTβR signaling is involved in renal injury and may be a suitable therapeutic target in renal diseases. More... »

PAGES

113-126

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ki.2015.280

    DOI

    http://dx.doi.org/10.1038/ki.2015.280

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1034003028

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26398497


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