T-BET/GATA-3 REGULATES TH1/TH2 IMBALANCE, PARTICIPATING IN RHEUMATOID ARTHRITIS RESPONSE

Guangyi Xiong, Jin Xu, Haibo Yin, Lina Xu, Ruilin Wang^*

Department of Pathology, Tianjin Hospital, Tianjin 300211, China

Objective: To analyse the role of the transcriptional regulatory factor (T-bet) and GATA connexin 3 (GATA-3) in inflammatory response and related mechanisms of rheumatoid arthritis (RA). 

Methods: Synovial tissue was obtained from RA patients and fibroblast-like synoviocytes (FLS) from patients in a control group. The synovial tissue from RA patients was divided into the RA model group and the T-bet interference group. The T-bet interference group was transfected with shRNA eukaryotic plasmids that inhibited T-bet expression. Enzyme-linked immunosorbent assay (ELISA) was used to detect Th1/Th2-related indexes in each group. Western blot analysis and immunohistochemistry showed that T cell-mediated T-bet, GATA-3, retinoic acid-related nuclear orphan receptor-γt (RORγt) and forkhead box protein 3 (FOXP3) levels were detected in each group. 

Results: The levels of INF-γ, TNF-α and IL-2 in the model group and the T-bet interference group were significantly higher than in the control group, while the levels of IL-4 were significantly lower than the control group. The levels of INF-γ, TNF-α and IL-2 in the T-bet interference group were significantly lower than the model group, and the levels of IL-4 were significantly higher than the model group (P<0.05). The level of RORγt protein in the model group and the T-bet interference group was significantly lower than the control group, the level of FOXP3 protein in the T-bet interference group was significantly higher than the model group, and the level of FOXP3 protein in the T-bet interference group was significantly lower than the model group (P<0.05). The level of GATA-3 protein in the model and the T-bet interference groups was significantly lower than the control group, the level of T-bet protein in model group was significantly higher than the control group, the level of GATA-3 protein in the T-bet interference group was significantly higher than the model group, and the level of T-bet protein was significantly lower in the model and control groups (P<0.05). 

Conclusion: Regulation of the T-bet/GATA-3 ratio can reduce inflammatory damage to RA cells, a mechanism that may be related to the regulation of the Th1/Th2 ratio of RA cells by T-bet.