Zhou H, Yang J Y, Xu P P, Liu L, Ding B J, Liu J P, Li M J, Song Y P
Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital) , Zhengzhou 450008, China.
Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Zhonghua Xue Ye Xue Za Zhi. 2021 Feb 14;42(2):146-150. doi: 10.3760/cma.j.issn.0253-2727.2021.02.010.
To explore the relationship between the expression of neuropilin-1 (NRP-1) on Treg cells and its ligands semaphorins-3A (Sema3A) , transforming growth factor-β(1) (TGF-β(1)) as well as the balance of type 1 helper T cells (Th(1)) and type 2 helper T cells (Th(2)) cells. This study enrolled 62 patients with immune thrombocytopenia (ITP; 33 and 29 newly diagnosed and chronic ITP, respectively) from March 2014 to May 2015. Consequently, 30 healthy people in the same period were selected as the normal control group. The expression of NRP-1 in Treg cells was detected via flow cytometry. The Sema3A, TGF-β(1), IFN-γ, and IL-4 levels in plasma were detected by enzyme-linked immunosorbent assay. The real-time polymerase chain reaction technique was used to detect the mRNA expression levels of NRP-1, Sema3A, and TGF-β(1). The one-way analysis of variance and independent sample t-test was used for comparison between three and two groups, respectively. Correlations among the mRNA expression levels of NRP-1, Sema3A, and TGF-β(1) were assessed via Spearman correlation coefficients. Treg cells in the newly diagnosed ITP group significantly increased compared with those in the chronic ITP and normal control groups. The expression of NRP-1 decreased[ (0.15 ± 0.03) %, (0.33 ± 0.15) %, and (0.46 ± 0.06) %; <0.01], the plasma Sema3A level increased[ (8.10 ± 1.32) μg/L, (7.41±1.30) μg/L, and (2.88±0.82) μg/L; <0.01], and the plasma TGF-β(1) level decreased[ (16.50±3.36) μg/L, (35.17±10.26) μg/L, and (41.00±10.02) μg/L; <0.01]. Moreover, the level of plasma IFN-γ increased[ (17.21+2.80) ng/L, (10.23+1.59) ng/L, and (8.18+3.27) ng/L; <0.01], and the ratios of Th(1)/Th(2) (IFN-γ/IL-4) increased (1.29±0.30, 0.72±0.16, and 0.61±0.27; <0.01) . The mRNA expressions of NRP-1 and Sema3A in the newly diagnosed ITP and chronic ITP groups were lower than that in the normal control group (<0.01) . Consequently, the NRP-1 mRNA expression was positively correlated with Sema3A and TGF-β(1) mRNA expression in the newly diagnosed ITP group. NRP-1 played an essential role in the pathogenesis of ITP.
探讨调节性T细胞（Treg细胞）上神经纤毛蛋白-1（NRP-1）的表达与其配体信号素-3A（Sema3A）、转化生长因子-β(1)（TGF-β(1)）以及1型辅助性T细胞（Th(1)）和2型辅助性T细胞（Th(2)）平衡之间的关系。本研究纳入了2014年3月至2015年5月期间62例免疫性血小板减少症（ITP）患者（分别为33例新诊断ITP患者和29例慢性ITP患者）。同时，选取同期30名健康人作为正常对照组。通过流式细胞术检测Treg细胞中NRP-1的表达。采用酶联免疫吸附测定法检测血浆中Sema3A、TGF-β(1)、干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）水平。运用实时聚合酶链反应技术检测NRP-1、Sema3A和TGF-β(1)的mRNA表达水平。分别采用单因素方差分析和独立样本t检验对三组和两组进行比较。通过Spearman相关系数评估NRP-1、Sema3A和TGF-β(1)的mRNA表达水平之间的相关性。新诊断ITP组的Treg细胞较慢性ITP组和正常对照组显著增加。NRP-1表达降低[分别为(0.15±0.03)%、(0.33±0.15)%和(0.46±0.06)%；P<0.01]，血浆Sema3A水平升高[分别为(8.10±1.32)μg/L、(7.41±1.30)μg/L和(2.88±0.82)μg/L；P<0.01]，血浆TGF-β(1)水平降低[分别为(16.50±3.36)μg/L、(35.17±10.26)μg/L和(41.00±10.02)μg/L；P<0.01]。此外，血浆IFN-γ水平升高[分别为(17.21+2.80)ng/L、(10.23+1.59)ng/L和(8.18+3.27)ng/L；P<0.01]，Th(1)/Th(2)（IFN-γ/IL-4）比值升高（分别为1.29±0.30、0.72±0.16和0.61±0.27；P<0.01）。新诊断ITP组和慢性ITP组中NRP-1和Sema3A的mRNA表达低于正常对照组（P<0.01）。因此，新诊断ITP组中NRP-1的mRNA表达与Sema3A和TGF-β(1)的mRNA表达呈正相关。NRP-1在ITP发病机制中起重要作用。
