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.

狼疮性肾炎 (LN) 是一种自身免疫性疾病，发病率/死亡率很高，可用疗法的疗效有限。记忆 T (Tm) 淋巴细胞浸润 LN 肾脏，导致器官损伤。对 LN、糖尿病肾病和健康供体肾活检的分析显示，在 LN中表达高电压依赖性 Kv1.3 钾通道（关键 T 细胞功能调节剂）的活性 CD8 ^{+ Tm 细胞高度浸润。}选择性下调 Tm 细胞中的 Kv1.3 (Kv1.3-NPs) 的纳米颗粒在体外降低了来自 LN 患者的 Tm 细胞中的 CD40L 和干扰素-γ (IFNγ)。通过将来自 LN 患者的外周血单个核细胞 (PBMC) 移植到免疫缺陷小鼠中获得的人源化 LN 小鼠中测试了 Kv1.3-NPs。LN 小鼠表现出疾病的特征：增加的 IFNγ 和 CD3 ⁺CD8 ⁺ T 细胞肾浸润，与健康供体 PBMC 移植小鼠相比，存活率降低。在移植前对患者 PBMC 进行 Kv1.3-NP 治疗可降低 CD40L/IFNγ 并延长 LN 小鼠的存活率。这些数据显示了在 LN 中定位 Kv1.3 的潜在好处。