The Changes In Peripheral Blood Th17 And Treg Ratios In Hashimoto’s Thyroiditis Are Accompanied By Differential PD-1/PD-L1 Expression

Background:Hashimoto’s thyroiditis(HT)is a kind of autoimmune diseases with organspecific characteristics.The pathogenesis is complex and related to many factors such as environment,heredity and autoimmune reaction.Both T helper 17cells(Th17s)and T regulatory cells(Tregs)belong to CD4~+T lymphocytes.Studies have found that the imbalance of T cell subsets affects the immune tolerance and immune stability of the body,and promotes the occurrence of Hashimoto’s thyroiditis.Programmed death receptor 1/Programmed death ligand 1(PD-1/PD-L1)is an immune checkpoint expressed on T cells.Enhancement or inhibition of this pathway is related to the immune process of Hashimoto’s thyroiditis.The paper mainly discusses the role of Th17/Treg cells and PD-1/PD-L1 pathway in Hashimoto’s thyroiditis.Objective:The aim of this study was to analyze the percentages of Th17s and Tregs in autoimmune Hashimoto’s thyroiditis(HT),and the expression of the checkpoint molecules PD-1/PD-L1 on these cells.Methods:Hashimoto’s thyroiditis patients and healthy controls were selected from the Endocrinology Clinic of the First Affiliated Hospital of Bengbu Medical College from April 2021 to September 2021.This is a case-control study involving 53initially diagnosed HT patients(HT group)and 21 normal controls(NC group).The peripheral blood mononuclear cells from the individuals of the two groups were isolated and restimulated ex vivo;the percentage of Th17s,Tregs,PD-1~+Th17s,PD-L1~+Th17s,PD-1~+Tregs,and PD-L1~+Tregs was assessed by flow cytometric analysis.Results:1.The percentage of Th17s in the peripheral blood of the HT group was significantly higher than that of the NC group[(6.38±1.32)%versus(3.12±0.66)%;t=14.110,P<0.001],while the percentage of peripheral blood Tregs was significantly lower[(3.82±1.48)%versus(5.61±1.60)%;t=-4.599,P<0.001].2.HT patients’Th17s expressed PD-1 at a significantly lower frequency than their counterparts in the NC[(6.46±2.77)%versus(18.51±3.96)%;t=-14.842,P<0.001],while no difference was observed for PD-L1 between the two groups.3.In contrast,both PD-1 and PD-L1 were expressed at significantly higher frequency on HT patients’Tregs than on NC[respectively:(17.01±3.04)%versus(10.23±2.77)%;t=8.850,P<0.001 for PD-1;(16.60±9.58)%versus(11.36±10.14)%;t=2.089,P<0.005,for PD-L1].Conclusion:1.The increased percentage of Th17s and decreased percentage of PD-1~+Th17s in the HT group suggest that a loss of control on Th17 activity through the checkpoint inhibitory axis PD-1/PD-L1 may participate in disease pathogenesis.2.While the decreased percentage of Tregs in HT patients may explain a lack of regulatory functions able to prevent the autoimmune destruction of the thyroid,the significance of the increased frequency of Tregs expressing PD-1 and PD-L1,previously reported to boost Tregs differentiation,remains to be established.Elucidating this apparent contradiction may reveal important mechanisms underlying HT pathogenesis.