Journal
SCIENCE ADVANCES
Volume 6, Issue 47, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abd1471
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Funding
- Dialysis Clinic Inc. Reserve fund
- Paul Teschan Research fund
- NIH [R01CA95286, AR070549]
- Cincinnati Children's Research Foundation Academic and Research Committee Award
- National Center for Advancing Translational Sciences of the NIH [2KL2TR001426-05A1]
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Lupus nephritis (LN) is an autoimmune disease with substantial morbidity/mortality and limited efficacy of available therapies. Memory T (Tm) lymphocytes infiltrate LN kidneys, contributing to organ damage. Analysis of LN, diabetic nephropathy, and healthy donor kidney biopsies revealed high infiltration of active CD8(+) Tm cells expressing high voltage-dependent Kv1.3 potassium channels-key T cell function regulators-in LN. Nanoparticles that selectively down-regulate Kv1.3 in Tm cells (Kv1.3-NPs) reduced CD40L and interferon-gamma (IFN gamma) in Tm cells from LN patients in vitro. Kv1.3-NPs were tested in humanized LN mice obtained by engrafting peripheral blood mononuclear cells (PBMCs) from LN patients into immune-deficient mice. LN mice exhibited features of the disease: increased IFNy and CD3(+)CD8(+)T cell renal infiltration, and reduced survival versus healthy donor PBMC engrafted mice. Kv1.3-NP treatment of patient PBMCs before engraftment decreased CD40L/IFN gamma and prolonged survival of LN mice. These data show the potential benefits of targeting Kv1.3 in LN.
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