Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Hong Kong, Hong Kong.
Department of Pathology, University of Hong Kong, Hong Kong.
Clin Immunol. 2015 Jan;156(1):43-57. doi: 10.1016/j.clim.2014.10.011. Epub 2014 Nov 13.
Tolerogenic dendritic cells (DCs) are potential cell-based therapy in autoimmune diseases. In this study, we generated alternatively activated DCs (aaDCs) by treating monocyte-derived DCs from patients with systemic lupus erythematosus (SLE) and healthy subjects with combination of 1,25 dihydroxyvitamin D(3) (vitD3) and dexamethasone followed by lipopolysaccharide-induced maturation. Lupus aaDCs were found to acquire semi-mature phenotype that remained maturation-resistant to immunostimulants. They produced low level of IL-12 but high level of IL-10. They had attenuated allostimulatory effects on T cell activation and proliferation comparable to normal aaDCs and demonstrated differential immunomodulatory effects on naïve and memory T cells. These aaDCs were capable of inducing IL-10 producing regulatory T effectors from naïve T cells whereas they modulated cytokine profile with suppressed production of IFN-γ and IL-17 by co-cultured memory T cells with attenuated proliferation. These aaDCs were shown to be superior to those generated using vitD3 alone in lupus patients.
耐受性树突状细胞(DCs)是自身免疫性疾病的一种潜在的细胞治疗方法。在这项研究中,我们通过用 1,25 二羟维生素 D(3)(vitD3)和地塞米松联合处理来自系统性红斑狼疮(SLE)患者和健康受试者的单核细胞来源的 DCs,随后用脂多糖诱导成熟,从而产生了替代性激活的 DCs(aaDCs)。狼疮 aaDCs 获得了半成熟表型,对免疫刺激剂仍然保持成熟抗性。它们产生低水平的 IL-12,但高水平的 IL-10。它们对 T 细胞活化和增殖的共刺激作用与正常 aaDCs 相当,并且对幼稚和记忆 T 细胞表现出不同的免疫调节作用。这些 aaDCs 能够从幼稚 T 细胞诱导产生 IL-10 产生的调节性 T 效应细胞,而它们通过与增殖减弱的记忆 T 细胞共培养来调节细胞因子谱,抑制 IFN-γ 和 IL-17 的产生。与单独使用 vitD3 相比,这些 aaDCs 在狼疮患者中显示出更好的效果。