Targeted knockdown of Kv1.3 channels in T lymphocytes corrects the disease manifestations associated with systemic lupus erythematosus

Sci Adv. 2020 Nov 18;6(47):eabd1471. doi: 10.1126/sciadv.abd1471. Print 2020 Nov.


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-γ (IFNγ) 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 IFNγ 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/IFNγ and prolonged survival of LN mice. These data show the potential benefits of targeting Kv1.3 in LN.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD40 Ligand
  • Gene Knockdown Techniques
  • Humans
  • Interferon-gamma
  • Kidney / pathology
  • Kv1.3 Potassium Channel* / genetics
  • Leukocytes, Mononuclear / pathology
  • Lupus Erythematosus, Systemic*
  • Lupus Nephritis* / etiology
  • Lupus Nephritis* / pathology
  • Mice
  • Nanoparticles
  • T-Lymphocytes*


  • Kv1.3 Potassium Channel
  • CD40 Ligand
  • Interferon-gamma