Yang Yanhui, Zhang Xian, Zhang Donglei, Li Huiyuan, Ma Li, Xuan Min, Wang Hongmei, Yang Renchi
1 Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
2 State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Clin Appl Thromb Hemost. 2017 Oct;23(7):786-792. doi: 10.1177/1076029616652726. Epub 2016 Jun 20.
Human monocytes are heterogeneous and play an important role in autoimmune diseases. However, the distribution and function of monocyte subsets remain unclear in primary immune thrombocytopenia (ITP). In this study, we determined the frequencies of monocyte subsets in 71 untreated patients with active ITP and 49 healthy controls by flow cytometry. Compared with controls, the frequency of nonclassical monocytes was significantly increased in patients with active ITP but decreased after complete remission. The intermediate subset was also increased in patients with active ITP and produced the highest levels of tumor necrosis factor α and interleukin 1β. Both the nonclassical and intermediate subsets were negatively correlated with the platelet counts. We further determined the correlation between monocyte subsets and the proliferation of platelet-autoreactive T cells. The purified monocyte subsets were cocultured with CD4 T cells and autologous platelets. The nonclassical subset showed the highest capability of promoting platelet reactive T-cell proliferation and significantly promoted the secretion of interferon γ among the 3 subsets. In conclusion, the nonclassical and intermediate monocyte subsets are both expanded and play different roles in the pathogenesis of ITP.
人类单核细胞具有异质性,在自身免疫性疾病中发挥重要作用。然而,在原发性免疫性血小板减少症(ITP)中,单核细胞亚群的分布和功能仍不清楚。在本研究中,我们通过流式细胞术测定了71例未经治疗的活动性ITP患者和49例健康对照者单核细胞亚群的频率。与对照组相比,活动性ITP患者中非经典单核细胞的频率显著增加,但在完全缓解后降低。中间亚群在活动性ITP患者中也增加,并产生最高水平的肿瘤坏死因子α和白细胞介素1β。非经典和中间亚群均与血小板计数呈负相关。我们进一步确定了单核细胞亚群与血小板自身反应性T细胞增殖之间的相关性。将纯化的单核细胞亚群与CD4 T细胞和自体血小板共培养。非经典亚群在3个亚群中表现出促进血小板反应性T细胞增殖的最高能力,并显著促进干扰素γ的分泌。总之,非经典和中间单核细胞亚群均扩增,并在ITP的发病机制中发挥不同作用。