Department of Hematology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China.
Thromb Res. 2013 Aug;132(2):196-201. doi: 10.1016/j.thromres.2013.04.025. Epub 2013 Jul 2.
Toll-like receptors have been found to be associated with immune-mediated diseases but it is still not clear whether they play a role in immune thrombocytopenic purpura (ITP), especially TLR4. CD4+ T-lymphocyte abnormalities, including Th17, Th1, Th2, and regulator T cell (Treg), are considered important in ITP. There have been few studies regarding the expression of TLR4 and the relationships between TLR4 and Th17 levels in ITP.
In this study, we evaluated the expression of TLR4 in monocytes, the plasma concentrations of IL-23, IL-17 and the profiles of Th17, Th1, Th2 cells in 70 patients with ITP and 31 healthy controls. In addition, we evaluated IL-2 and Treg cells in 46 cases of 70 patients with ITP and the same 31 controls.
Higher levels of TLR4 expression, higher relative numbers of Th17 and Th1 cells and lower levels of Treg cells were observed in patients when compared with controls (p=0.001 for TLR4; p<0.001 for Th17; p=0.014 for Th1; p=0.001 for Treg). The levels of IL-23 and IL-2 were increased (p=0.022 for IL-23; p=0.025 for IL-2), the relative levels of Th2 and concentrations of IL-17 were similar across both groups (p=0.446 for Th2; p=0.316 for IL-17). A significant negative correlation was observed between levels of TLR4 and Treg(r=-0.544, p<0.001), but a significantly positive correlation was observed between IL-2 and IL-23 concentration in patients (r=0.441, p=0.004). Neither the correlation between TLR4 and the other CD4(+) T cells and cytokines nor the correlation between the three cytokines and CD4+ T cells was found to be statistically significant.
Our data showed that TLR4, CD4+ T cells (Th1, Th17 and Treg cells) and related cytokines (IL-23, IL-2) may take part in the pathogenesis of ITP. TLR4 may play a role through the TLR4-cytokine-CD4+ T lymphocyte cell pathway.
Toll 样受体已被发现与免疫介导的疾病有关,但尚不清楚它们是否在免疫性血小板减少性紫癜(ITP)中发挥作用,尤其是 TLR4。CD4+T 淋巴细胞异常,包括 Th17、Th1、Th2 和调节性 T 细胞(Treg),被认为在 ITP 中很重要。关于 TLR4 的表达以及 TLR4 与 ITP 中 Th17 水平之间的关系,研究甚少。
本研究评估了 70 例 ITP 患者和 31 例健康对照者外周血单核细胞 TLR4 的表达、血浆 IL-23、IL-17 浓度以及 Th17、Th1、Th2 细胞的特征。此外,我们还评估了 70 例 ITP 患者中的 46 例 IL-2 和 Treg 细胞与相同的 31 例对照者的 IL-2 和 Treg 细胞。
与对照组相比,患者 TLR4 表达水平更高,Th17 和 Th1 细胞相对数量更高,Treg 细胞水平更低(p=0.001 用于 TLR4;p<0.001 用于 Th17;p=0.014 用于 Th1;p=0.001 用于 Treg)。IL-23 和 IL-2 水平升高(p=0.022 用于 IL-23;p=0.025 用于 IL-2),两组间 Th2 相对水平和 IL-17 浓度相似(p=0.446 用于 Th2;p=0.316 用于 IL-17)。患者中 TLR4 水平与 Treg 呈显著负相关(r=-0.544,p<0.001),但患者中 IL-2 与 IL-23 浓度呈显著正相关(r=0.441,p=0.004)。未发现 TLR4 与其他 CD4+T 细胞和细胞因子之间的相关性,也未发现三种细胞因子与 CD4+T 细胞之间的相关性具有统计学意义。
我们的数据表明,TLR4、CD4+T 细胞(Th1、Th17 和 Treg 细胞)及其相关细胞因子(IL-23、IL-2)可能参与了 ITP 的发病机制。TLR4 可能通过 TLR4-细胞因子-CD4+T 淋巴细胞途径发挥作用。