Regulation of Th1/Th2 and Th17/Treg by pDC/mDC imbalance in primary immune thrombocytopenia

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.

The Value of Combined Detection of Megakaryocyte and Platelet Parameters for the Diagnosis of Primary Immune Thrombocytopenia

“…ITP was thought to occur primarily due to antibody-mediated autoimmune diseases. Current studies 1 , 2 have reported that cellular immunity also plays a role in the pathogenesis of ITP. T cells especially play an important role in pathogenesis.…”

Effective biomarkers and therapeutic targets of nerve-immunity interaction in the treatment of depression: an integrated investigation of the miRNA-mRNA regulatory networks

“…Chemokines, which include Th17, Th1, and Th2, are key chemicals in the immunological and neurological systems. They can coordinate this migration of T and B cells to inflammatory areas, promote T cell activity and help B cell activation, and play a role in regulating immunity-inflammation in the immune system [ 66 ]. Following psychological stress, activated T cells can enter the central nervous system in a variety of ways, reduce inflammation, and support neuronal integrity via cellular immunity, thus modifying depressed behavior [ 67 ].…”

Diagnostic Value of Peripheral Blood Lymphocytes for Primary Immune Thrombocytopenia

“…In this study, a series of findings suggest that lymphocyte levels were closely associated with the development and progression of primary immune thrombocytopenia. This may be due to the fact that (1) lymphocytes are a type of leukocyte, produced mainly by lymphoid organs, are an important cellular component of the body's immune response function, and are the main performers of the immune function [ 9 , 10 ]. In terms of physiology, but in the presence of pathogenic microorganisms, cancer cells, and allogeneic cells in the human body, lymphatic T cells and B cells were transformed and differentiated into allergenic T lymphocytes, plasma cells, and immunoglobulins to remove the invading substances, participate in humoral immunity and reduce the degree of damage to the organism, while NK cells have the role of killing target cells and are important in promoting the recovery of the inflammatory response and maintaining the health of the organism [ 11 ].…”