Imbalance of follicular regulatory T (Tfr) cells/follicular helper T (Tfh) cells in adult patients with primary immune thrombocytopenia

Abstract

This study is to investigate the role of follicular regulatory T (Tfr) cells/follicular helper T (Tfh) cells imbalance in adult patients with primary immune thrombocytopenia (ITP). Totally, 40 cases of primary ITP patients and 30 healthy controls were enrolled. Blood samples were collected from ITP patients (pre- and post-therapy) and controls. Flow cytometry was used to detect the proportion of Tfr and Tfh cells in peripheral blood. Real-time quantitative polymerase chain reaction (PCR) was performed to detect the mRNA expression levels of FOXP3, BCL-6, and BLIMP-1. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect interleukin (IL)-10 and IL-21 levels. Spearman’s correlation was used for correlation analysis. Compared with control, Tfr cell proportion, FOXP3 mRNA, and IL-10 were significantly decreased in the pre-therapy ITP group, but were significantly increased post-therapy. Tfh cell proportion, BCL-6 mRNA, and IL-21 were increased, while BLIMP-1 mRNA was decreased, in the pre-therapy ITP group than the control group. These effects were reversed in the post-therapy ITP group. Moreover, the Tfr/Tfh ratio was decreased in the pre-therapy ITP group than control group, whereas was increased in the post-therapy ITP group than the pre-therapy ITP group. Furthermore, Tfr cell proportion, FOXP3 mRNA, IL-10, and Tfr/Tfh ratio were positively correlated with the platelet count (PLT) in the ITP pre-therapy group. In addition, Tfh cell proportion, BCL-6 mRNA, and IL-21 were negatively correlated with the PLT, while BLIMP-1 mRNA was positively correlated with the PLT. Conclusively, Tfr cell proportion in peripheral blood is decreased and Tfh cell proportion is increased, leading to unbalanced Tfr/Tfh ratio in ITP patients pre-therapy. The imbalance of Tfr/Tfh is recovered post-therapy, suggesting that the Tfr and Tfh cells may be involved in ITP pathogenesis. The abnormal expression of FOXP3, BCL-6, and BLIMP-1 mRNA and the changes in IL-10 and IL-21 levels may be related to the imbalance of Tfr/Tfh.

The miR-641-STIM1 and SATB1 axes play important roles in the regulation of the Th17/Treg balance in ITP

“…The destruction of platelets in ITP occurs primarily through two mechanisms: antibody-mediated clearance by the spleen and immune-mediated damage to megakaryocytes. The currently known T cells dysfunctions of ITP includes T-cell toxicity 1 , abnormal regulatory T cells [2][3][4] , an imbalance in helper T cells 5,6 , abnormal T-cell responses 7,8 . A growing body of research suggests that the Treg/Th17 balance plays a key role in the development of ITP 4,[9][10][11] .…”