Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia
Qinzhi Li, Yang Liu, Xiujuan Wang, Mingling Sun, Lei Wang, Xinyou Wang, Ying Liu, Wenxia Fan, Kaile Zhang, Xiao Sui, Xinhong Guo
Abstract
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 ( P = 0.004), while the mDC proportion was not significantly changed ( P = 0.681), resulting in a decrease in the pDC/mDC ratio ( P = 0.001). Additionally, compared with controls, serum levels of interleukin (IL)-6, IL-12, and IL-23 were increased in ITP patients ( P < 0.001), and mRNA levels of IL-12p40, IL-12p35, and IL-23p19 were also increased ( P =0.014, P = 0.043, P < 0.001). Compared with the healthy control, the proportion of Th1 and Th17 cells in ITP patients increased ( P = 0.001, P = 0.031). Serum levels of interferon gamma (IFN-γ) and IL-17 in ITP patients also increased ( P = 0.025, P = 0.005). Furthermore, T-bet and RORγt mRNA levels were increased in peripheral blood of ITP patients ( P = 0.018, P < 0.001). Correspondingly, the proportion of Th2 and Treg cells decreased ( P = 0.007, P < 0.001), along with a decrease in serum IL-4 and transforming growth factor beta (TGF-β) ( P = 0.028, P = 0.042), and an increase in GATA-3 mRNA ( P < 0.001). However, there was no significant difference in Foxp3 mRNA levels ( P = 0.587). Pearson correlation analysis showed that the proportion of total dendritic cells (DCs) was positively correlated with IL-12 ( r = 0.526, P = 0.003) and IL-23 ( r = 0.501, P = 0.005) in ITP patients. Th1/Th2 ratio, IFN-γ, and IL-12 levels were negatively correlated with platelet counts ( r = −0.494, P = 0.009; r = –0.415, P = 0.028; r = –0.492, P = 0.032). However, IL-23 was positively correlated with IL-17 ( r = 0.489, P = 0.006) and negatively correlated with platelet count ( r = –0.564, P = 0.001). The ratio of IL-6 and Th17 cells was negatively correlated with platelet count ( r = –0.443, P = 0.014; r = –0.471, P = 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.