The programmed death-1 (PD-1) pathway has been shown to deliver an inhibitory signal, and aberrant expression of the PD-1 molecule and/or its ligand programmed death ligand 1 (PD-L1) has been demonstrated in human diseases, while its other ligand, programmed death ligand 2 (PD-L2), has rarely been studied. Here, we investigated the expression of PD-L2 in synovial tissue and blood from patients with rheumatoid arthritis (RA). Soluble PD-L2 and inflammatory cytokine levels in serum among healthy controls and patients with RA were compared via enzyme-linked immunosorbent assay (ELISA). Membrane PD-L2 on monocytes in blood was analyzed through flow cytometry (FCM). The different expression levels of PD-L2 between the RA and non-RA synovium were semi-quantified by immunohistochemical (IHC) staining. The soluble PD-L2 levels in serum from patients with RA were significantly lower than those in healthy subjects, correlating with active parameters (rheumatoid factor) and inflammatory cytokine secretion. The FCM results showed that patients with RA had significantly increased percentages of PD-L2-expressing CD14⁺ monocytes and correlated with inflammatory cytokines. PD-L2 expression on macrophages in the synovium from patients with RA was recorded by IHC staining with a higher score, and its correlation with pathological scores and clinical features was determined. Together, our results revealed aberrant expression of PD-L2 in RA, which may be a promising biomarker and therapeutic target associated with the pathogenesis of RA.

程序性死亡 1 (PD-1) 途径已被证明可以传递抑制信号，并且 PD-1 分子和/或其配体程序性死亡配体 1 (PD-L1) 的异常表达已在人类疾病中得到证实。而它的另一个配体，程序性死亡配体2 (PD-L2)，却很少被研究。在这里，我们研究了类风湿性关节炎 (RA) 患者滑膜组织和血液中 PD-L2 的表达。通过酶联免疫吸附测定（ELISA）比较健康对照和 RA 患者血清中可溶性 PD-L2 和炎性细胞因子水平。通过流式细胞术 (FCM) 分析血液中单核细胞上的膜 PD-L2。通过免疫组织化学 (IHC) 染色半定量 RA 和非 RA 滑膜之间 PD-L2 的不同表达水平。RA 患者血清中可溶性 PD-L2 水平显着低于健康受试者，与活性参数（类风湿因子）和炎症细胞因子分泌相关。FCM 结果显示，RA 患者表达 PD-L2 的 CD14 ⁺单核细胞的百分比显着增加，并与炎症细胞因子相关。通过 IHC 染色记录评分较高的 RA 患者滑膜巨噬细胞上的 PD-L2 表达，并确定其与病理评分和临床特征的相关性。总之，我们的结果揭示了 RA 中 PD-L2 的异常表达，这可能是与 RA 发病机制相关的有前途的生物标志物和治疗靶点。