Department of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
Arthritis Res Ther. 2010;12(4):R137. doi: 10.1186/ar3075. Epub 2010 Jul 9.
Dendritic cells (DCs) are capable of inducing immunity or tolerance. Previous studies have suggested plasmacytoid DCs (pDCs) are pathogenic in systemic lupus erythematosus (SLE). However, the functional characteristics of directly isolated peripheral circulating blood pDCs in SLE have not been evaluated previously.
Peripheral blood pDCs from 62 healthy subjects and 58 SLE patients were treated with apoptotic cells derived from polymorphonuclear cells (PMNs). Antigen loaded or unloaded pDCs were then co-cultured with autologous or allogenous T cells. Changes in T cell proliferation, cell surface CD25 expression, intracellular Foxp3 expression and cytokine production were evaluated. pDCs that had captured apoptotic PMNs (pDCs + apoPMNs were also studied for their cytokine production (interferon (IFN)-alpha, interleukin (IL)-6, IL-10, IL-18) and toll like receptor (TLR) expression.
Circulating pDCs from SLE patients had an increased ability to stimulate T cells when compared with control pDCs. Using allogenous T cells as responder cells, SLE pDCs induced T cell proliferation even in the absence of apoptotic PMNs. In addition, healthy pDCs + apoPMNs induced suppressive T regulatory cell features with increased Foxp3 expression in CD4 + CD25 + cells while SLE pDCs + apoPMNs did not. There were differences in the cytokine profile of pDCs that had captured apoptotic PMNs between healthy subjects and patients with SLE. Healthy pDCs + apoPMNs showed decreased production of IL-6 but no significant changes in IL-10 and IL-18. These pDCs + apoPMNs also showed increased mRNA transcription of TLR9. On the other hand, while SLE pDCs + apoPMNs also had decreased IL-6, there was decreased IL-18 mRNA expression and persistent IL-10 protein synthesis. In addition, SLE pDCs lacked TLR9 recruitment.
We have demonstrated that peripheral circulating pDCs in patients with SLE were functionally abnormal. They lacked TLR9 expression, were less capable of inducing regulatory T cell differentiation and had persistent IL-10 mRNA expression following the capture of apoptotic PMNs. We suggest circulating pDCs may be pathogenically relevant in SLE.
树突状细胞（DCs）能够诱导免疫或耐受。先前的研究表明浆细胞样树突状细胞（pDCs）在系统性红斑狼疮（SLE）中是致病的。然而，以前尚未评估过直接从 SLE 患者外周循环血中分离的外周循环血 pDC 的功能特征。
用多形核细胞（PMN）来源的凋亡细胞处理 62 名健康受试者和 58 名 SLE 患者的外周血 pDC。然后将负载或未负载抗原的 pDC 与自体或同种异体 T 细胞共培养。评估 T 细胞增殖、细胞表面 CD25 表达、细胞内 Foxp3 表达和细胞因子产生的变化。还研究了捕获凋亡 PMN 的 pDC（pDCs+apoPMNs）的细胞因子产生（干扰素（IFN）-α、白细胞介素（IL）-6、IL-10、IL-18）和 Toll 样受体（TLR）表达。
与健康对照 pDC 相比，SLE 患者的循环 pDC 刺激 T 细胞的能力增强。使用同种异体 T 细胞作为反应细胞，即使在没有凋亡 PMN 的情况下，SLE pDC 也能诱导 T 细胞增殖。此外，健康 pDCs+apoPMNs 诱导 CD4+CD25+细胞中 Foxp3 表达增加的抑制性 T 调节细胞特征，而 SLE pDCs+apoPMNs 则没有。健康受试者和 SLE 患者中捕获凋亡 PMN 的 pDC 的细胞因子谱存在差异。健康 pDCs+apoPMNs 显示 IL-6 产生减少，但 IL-10 和 IL-18 无明显变化。这些 pDCs+apoPMNs 还显示 TLR9 的 mRNA 转录增加。另一方面，虽然 SLE pDCs+apoPMNs 也减少了 IL-6，但 IL-18 的 mRNA 表达减少且持续产生 IL-10 蛋白。此外，SLE pDCs 缺乏 TLR9 募集。
我们已经证明 SLE 患者的外周循环 pDC 功能异常。它们缺乏 TLR9 表达，诱导调节性 T 细胞分化的能力降低，并且在捕获凋亡 PMN 后持续表达 IL-10 mRNA。我们认为循环 pDC 可能与 SLE 中的病原体有关。
