原发免疫性血小板减少症中 pDC/mDC 失衡对 Th1/Th2 和 Th17/Treg 的调控作用。
Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia.
机构信息
Hematologic Disease Center, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region Research Institute of Hematology, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region,830011, China.
出版信息
Exp Biol Med (Maywood). 2021 Aug;246(15):1688-1697. doi: 10.1177/15353702211009787. Epub 2021 May 2.
This study investigates the regulatory effect of plasmacytoid dendritic cells (pDC)/myeloid dendritic cells (mDC) imbalance on balance of Th1/Th2 and Th17/Treg in primary immune thrombocytopenia (ITP). A total of 30 untreated ITP patients and 20 healthy controls were recruited. Compared with healthy control, the pDC proportion of ITP patients was significantly reduced ( = 0.004), while the mDC proportion was not significantly changed ( = 0.681), resulting in a decrease in the pDC/mDC ratio ( = 0.001). Additionally, compared with controls, serum levels of interleukin (IL)-6, IL-12, and IL-23 were increased in ITP patients ( < 0.001), and mRNA levels of IL-12p40, IL-12p35, and IL-23p19 were also increased ( =0.014, = 0.043, < 0.001). Compared with the healthy control, the proportion of Th1 and Th17 cells in ITP patients increased ( = 0.001, = 0.031). Serum levels of interferon gamma (IFN-γ) and IL-17 in ITP patients also increased ( = 0.025, = 0.005). Furthermore, T-bet and RORγt mRNA levels were increased in peripheral blood of ITP patients ( = 0.018, < 0.001). Correspondingly, the proportion of Th2 and Treg cells decreased ( = 0.007, < 0.001), along with a decrease in serum IL-4 and transforming growth factor beta (TGF-β) ( = 0.028, = 0.042), and an increase in GATA-3 mRNA ( < 0.001). However, there was no significant difference in Foxp3 mRNA levels ( = 0.587). Pearson correlation analysis showed that the proportion of total dendritic cells (DCs) was positively correlated with IL-12 ( = 0.526, = 0.003) and IL-23 (= 0.501, = 0.005) in ITP patients. Th1/Th2 ratio, IFN-γ, and IL-12 levels were negatively correlated with platelet counts ( = -0.494, = 0.009; = -0.415, = 0.028; = -0.492, = 0.032). However, IL-23 was positively correlated with IL-17 (= 0.489, = 0.006) and negatively correlated with platelet count ( = -0.564, = 0.001). The ratio of IL-6 and Th17 cells was negatively correlated with platelet count ( = -0.443, = 0.014; = -0.471, = 0.011). The imbalance of pDC/mDC and the increase of IL-6, IL-12, and IL-23 lead to the increased differentiation of CD4+ T cells into Th1 and Th17 cells, which might be the important mechanisms underlying the imbalance of Th1/Th2 and Th17/Treg in ITP patients.
本研究探讨了浆细胞样树突状细胞（pDC）/髓样树突状细胞（mDC）失衡对原发性免疫性血小板减少症（ITP）患者中 Th1/Th2 和 Th17/Treg 平衡的调节作用。共招募了 30 例未经治疗的 ITP 患者和 20 名健康对照者。与健康对照组相比，ITP 患者的 pDC 比例显著降低（=0.004），而 mDC 比例无明显变化（=0.681），导致 pDC/mDC 比值降低（=0.001）。此外，与对照组相比，ITP 患者血清白细胞介素（IL）-6、IL-12 和 IL-23 水平升高（<0.001），IL-12p40、IL-12p35 和 IL-23p19 的 mRNA 水平也升高（=0.014、=0.043、<0.001）。与健康对照组相比，ITP 患者 Th1 和 Th17 细胞的比例增加（=0.001、=0.031）。ITP 患者血清干扰素γ（IFN-γ）和 IL-17 水平也升高（=0.025、=0.005）。此外，ITP 患者外周血 T-bet 和 RORγt mRNA 水平升高（=0.018、<0.001）。相应地，Th2 和 Treg 细胞的比例降低（=0.007、<0.001），同时血清 IL-4 和转化生长因子β（TGF-β）水平降低（=0.028、=0.042），GATA-3 mRNA 水平升高（<0.001）。然而，Foxp3 mRNA 水平没有显著差异（=0.587）。Pearson 相关分析显示，总树突状细胞（DCs）的比例与 ITP 患者的 IL-12（=0.526、=0.003）和 IL-23（=0.501、=0.005）呈正相关。Th1/Th2 比值、IFN-γ 和 IL-12 水平与血小板计数呈负相关（=−0.494、=0.009；=−0.415、=0.028；=−0.492、=0.032）。然而，IL-23 与 IL-17 呈正相关（=0.489、=0.006），与血小板计数呈负相关（=−0.564、=0.001）。IL-6 和 Th17 细胞的比值与血小板计数呈负相关（=−0.443、=0.014；=−0.471、=0.011）。pDC/mDC 的失衡和 IL-6、IL-12 和 IL-23 的增加导致 CD4+T 细胞向 Th1 和 Th17 细胞的分化增加，这可能是 ITP 患者 Th1/Th2 和 Th17/Treg 失衡的重要机制。
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