The Relationship Between SOCS1/3 And Th17 Cells And Their Role In Hashimoto’s Thyroiditis

Objective:To investigate the levels of Th17 cells and RORγt in patients with HT, analyze the relations between Th17 cells and auto-antibodies, evaluate the role of Thl7 cells and related cytokines in the pathogenesis of patients with HT.To investigate the role of SOCS1 and SOCS3 and STAT3 in regulation of T cell differentiation in hashimoto thyroiditis.Methods:1.Thirty patients with HT, thirty patients with GD and thirty healthy controls were studied in October 2014 to May 2016 period.2.QRT-PCR was used to measure the expression of SOCS1 m RNA,SOCS3 m RNA, STAT3 m RNA and RORγt m RNA in PBMC.The frequency of CD4+Tcells in PBMC was analyzed by flow cytometry(FCM).Finding the CD4+ and IL-17+T cells which is Th17 cells, and the proportion of Th17 cells was measured.The concentrations of SOCS1 protein, SOCS3 protein and STAT3 protein were measured by enzyme-linked immunosorbent assay(ELISA).3.The levels of thyroid hormones(FT3, FT4, TSH), TG-Ab and TPO-Ab were detected by chemiluminescence, used the correlation analysis to understand the relationship between Th17 and the levels of auto-antibodies.Results:1. Compared with normal control group, the percentage of Th17 cells was obviously higher in HT group(p < 0.05); The percentage of Th17 cells was significantly higher in GD group compared with normal control group(p < 0.05);There was a distinct increase inthe percentage of Th17 cells in HT group compared with GD group(p<0.05).2. The levels of RORγt m RNA, SOCS1 m RNA and SOCS3 m RNA was obviously increased in HT group compared with normal control group(all p<0.05);However, the levels of STAT3 m RNA was clearly decreased in HT group comparedwith normal control group(p<0.05). There was a distinct increase in the levels of RORγt m RNA, SOCS1 m RNA and SOCS3 m RNA in GD group compared with normal control group(all p < 0.05);But the levels of STAT3 m RNA was clearly decreased in GD group compared with normal control group(p <0.05).There was significant differences in the levels of RORγt m RNA, SOCS1 m RNA, SOCS3 m RNA and STAT3 m RNA among the two samples of HT and GD;Further comparisons between two groups of samples significantly increased levels of RORγt m RNA and SOCS1 m RNA and SOCS3 m RNA from HT group to GD group(all p < 0.05);Conversely, a significantly decreased was found in STAT3 m RNA expression(p<0.05).3.The concentrations of SOCS1 protein and SOCS3 protein were obviously increased in HT group compared with normal control group(all p<0.05);However,the concentration of STAT3 protein was clearly decreased in HT group compared with normal control group(p < 0.05). The concentrations of SOCS1 protein and SOCS3 protein was clearly reduced in GD group compared with the HT group and normal control groups(p < 0.05); But the concentration of STAT3 protein was significantly increased in GD group compared with the HT group and normal control groups(p<0.05).4. There were no significant correlation between Th17 cells and the levels of TG-Ab(r=0.003, p > 0.05); And positive correlations were found between the percentage of Th17 cells and the levels of TPO-Ab(r=0.493, p<0.05).Conclusions:1. The percentage of Th17 cells and specific transcription factors RORγt were increased in patients with hashimoto thyroiditis.The percentage of Th17 cells was positively correlated with the level of TPO-Ab.2. The levels of SOCS1 m RNA and SOCS3 m RNA were obviously increased,and the level of STAT3 m RNA was significantly decreased in HT patients. The concentrations of SOCS1 protein and SOCS3 protein were significantly increased,and the concentrations of STAT3 protein was significantly decreased in HT patients.SOCS1 and SOCS3 may play critical roles in inhibiting the differentiation of Th17 cells by inhibiting JAK-STAT3 signaling pathway in HT. However, theinhibitory effect of SOCS1 and SOCS3 were not fully offset the auxo-action which caused by IL-17 and so on. Thus Th17 cells was maintained higher level for a long time, the inflammatory reaction of thyroid tissues has always existed. Therefor SOCS1 and SOCS3 play an important role in thyroid inflammation hashimoto.3. The changes of SOCS1, SOCS3 m RNA in HT were consistent with the changes of its protein. There was significant differences in these changes in HT compared with GD that belongs to autoimmune thyroid disease. It is speculated that there was some kind of epigenetic modification both of them, but the degree of epigenetic modification was different.