OBJECTIVES Mesenchymal stromal cells (MSCs) and low-dose interleukin-2 (IL-2) both have demonstrated efficacy in treating systemic lupus erythematosus (SLE). The aim of this study is to conduct a head-to-head comparison between the 2 treatments and provide insights for clinical applications. METHODS Lupus-prone mice were treated with umbilical cord-derived MSCs (UC-MSCs), IL-2, or a combination of UC-MSCs and IL-2, respectively. The lupus-like symptoms, renal pathology, and T-cell response were assessed 1 or 4 weeks later. Modulation of IL-2 production by MSCs on immune cells was investigated by the coculture assay. Disease activity and serum IL-2 of SLE patients were determined before and after receiving UC-MSCs. RESULTS Both UC-MSCs and IL-2 improved lupus symptoms in lupus-prone mice 1 week after treatment, while the effects of UC-MSCs lasted up to 4 weeks. Moreover, the UC-MSC-treated group showed better renal pathology improvement. Importantly, UC-MSCs combined with IL-2 did not provide better efficacy than UC-MSCs alone. Consistent with this, UC-MSCs alone and UC-MSCs + IL-2 resulted in similar levels of serum IL-2 and frequencies of Tregs. Neutralization of IL-2 partly reduced the promotion of Tregs by UC-MSCs, suggesting that IL-2 was involved in the upregulation of Tregs by UC-MSCs. Lastly, an increase in serum IL-2 positively correlated with the reduction of disease activity of SLE patients by UC-MSCs. CONCLUSION Both the single injection of UC-MSCs and repeated IL-2 administration exerted comparable efficacy in alleviating SLE manifestations, but UC-MSCs provided sustained alleviation and showed better improvement in renal pathology.

中文翻译：

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与低剂量白细胞介素 2 相比，同种异体脐带来源的间充质基质细胞在系统性红斑狼疮中维持长期治疗效果。

目的 间充质基质细胞 (MSC) 和低剂量白细胞介素 2 (IL-2) 均已证明对治疗系统性红斑狼疮 (SLE) 有效。本研究的目的是对两种治疗方法进行头对头比较，并为临床应用提供见解。方法 分别用脐带源性间充质干细胞 (UC-MSC)、IL-2 或 UC-MSC 和 IL-2 的组合治疗易患狼疮的小鼠。1 或 4 周后评估狼疮样症状、肾脏病理学和 T 细胞反应。通过共培养测定研究了 MSC 对免疫细胞产生 IL-2 的调节。在接受UC-MSCs之前和之后测定SLE患者的疾病活动度和血清IL-2。结果 治疗 1 周后，UC-MSC 和 IL-2 均改善了易患狼疮的小鼠的狼疮症状。而UC-MSCs的效果可持续长达4周。此外，UC-MSC治疗组表现出更好的肾脏病理改善。重要的是，UC-MSC 联合 IL-2 并没有比单独使用 UC-MSC 提供更好的疗效。与此一致的是，单独的 UC-MSC 和 UC-MSC + IL-2 导致血清 IL-2 水平和 Tregs 频率相似。IL-2的中和部分降低了UC-MSC对Treg的促进作用，表明IL-2参与了UC-MSC对Treg的上调。最后，血清 IL-2 的增加与 UC-MSC 降低 SLE 患者疾病活动度呈正相关。结论 单次注射UC-MSCs和重复注射IL-2在缓解SLE表现方面的疗效相当，但UC-MSCs提供了持续的缓解效果，并且对肾脏病理有更好的改善。