Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). Multiple immunomodulatory mechanisms contribute to the pathogenesis of LN. A deep understanding of the immunopathogenesis of LN is essential to identify optimal molecular targets, as most immunotherapeutic algorithms are still based on unselective drugs. The study aimed to elucidate the possible association of vitamin D deficiency with the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis and inflammatory response in patients with LN, as well as the relationship between the PD-1/PD-L1 axis and chemokine C-X-C motif ligand 12 (CXCL12). Flow cytometry was used to determine the frequencies of CD279 (PD-1) and CD274 (PD-L1) in the peripheral CD3+CD4+ cell population of persons with LN. Furthermore, ELISA was used to detect serum CXCL12 and vitamin D concentrations. A distinct decrease of PD-1 and a significant increase of PD-L1 was demonstrated in patients with LN compared with either SLE patients with no LN or healthy controls. The PD-1/PD-L1 axis was negatively correlated with different disease parameters. Vitamin D deficiency and insufficiency were more prevalent in patients with LN than in controls, being significantly associated with disease activity and inversely associated with the PD-1/PD-L1 expression. Moreover, CXCL12 was negatively correlated with the PD-1/PD-L1 axis and vitamin D concentration. The findings suggest an involvement of the PD-1/PD-L1 axis in lupus nephritis, which might serve as a potential highly selective therapeutic target that is more effective but less toxic. In addition, restoring adequate vitamin D levels in lupus nephritis could be a possible simple measure to control inflammatory immune responses.

中文翻译：

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狼疮肾炎 CD4+ T 细胞的免疫调节轴（程序性死亡 1/程序性死亡配体 1）：与维生素 D 和趋化因子 CXC 基序配体 12 的关联

狼疮性肾炎（LN）是系统性红斑狼疮（SLE）最严重的并发症之一。多种免疫调节机制有助于 LN 的发病机制。深入了解 LN 的免疫发病机制对于确定最佳分子靶点至关重要，因为大多数免疫治疗算法仍然基于非选择性药物。本研究旨在阐明维生素 D 缺乏与 LN 患者程序性死亡 1（PD-1）/程序性死亡配体 1（PD-L1）轴和炎症反应的可能关联，以及两者之间的关系。 PD-1/PD-L1 轴和趋化因子 CXC 基序配体 12 (CXCL12)。流式细胞术用于确定 LN 患者外周 CD3+CD4+ 细胞群中 CD279 (PD-1) 和 CD274 (PD-L1) 的频率。此外，ELISA用于检测血清CXCL12和维生素D浓度。与没有 LN 的 SLE 患者或健康对照相比，LN 患者的 PD-1 明显减少和 PD-L1 显着增加。PD-1/PD-L1轴与不同的疾病参数呈负相关。与对照组相比，LN 患者的维生素 D 缺乏和不足更为普遍，与疾病活动显着相关，与 PD-1/PD-L1 表达呈负相关。此外，CXCL12 与 PD-1/PD-L1 轴和维生素 D 浓度呈负相关。研究结果表明 PD-1/PD-L1 轴参与狼疮肾炎，这可能作为一种潜在的高选择性治疗靶点，更有效但毒性更小。此外，