The changes in peripheral blood Th17 and Treg ratios in Hashimoto’s thyroiditis are accompanied by differential PD-1/PD-L1 expression

ObjectiveThe aim of this study was to analyze the percentages of T helper 17 cells (Th17s) and T regulatory cells (Tregs) in autoimmune Hashimoto’s thyroiditis (HT), and the expression of the checkpoint molecules programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) on these cells.Metho...

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Main Authors: Jun Fang, Lei Yu, Lan-Gen Zhuang, Xiao-Yan Pei, Qiong Wang, Guo-Xi Jin
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2022.959477/full
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author Jun Fang
Lei Yu
Lan-Gen Zhuang
Xiao-Yan Pei
Qiong Wang
Guo-Xi Jin
author_facet Jun Fang
Lei Yu
Lan-Gen Zhuang
Xiao-Yan Pei
Qiong Wang
Guo-Xi Jin
author_sort Jun Fang
collection DOAJ
description ObjectiveThe aim of this study was to analyze the percentages of T helper 17 cells (Th17s) and T regulatory cells (Tregs) in autoimmune Hashimoto’s thyroiditis (HT), and the expression of the checkpoint molecules programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) on these cells.MethodsThis is a case-control study involving 53 initially 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.
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spelling doaj.art-48cad722b17e46d2ace4b15f373c94012022-12-22T01:28:21ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-08-011310.3389/fendo.2022.959477959477The changes in peripheral blood Th17 and Treg ratios in Hashimoto’s thyroiditis are accompanied by differential PD-1/PD-L1 expressionJun FangLei YuLan-Gen ZhuangXiao-Yan PeiQiong WangGuo-Xi JinObjectiveThe aim of this study was to analyze the percentages of T helper 17 cells (Th17s) and T regulatory cells (Tregs) in autoimmune Hashimoto’s thyroiditis (HT), and the expression of the checkpoint molecules programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) on these cells.MethodsThis is a case-control study involving 53 initially 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.https://www.frontiersin.org/articles/10.3389/fendo.2022.959477/fullPD-1PD-L1Hashimoto’s thyroiditisT helper 17 cellsT regulatory cells
spellingShingle Jun Fang
Lei Yu
Lan-Gen Zhuang
Xiao-Yan Pei
Qiong Wang
Guo-Xi Jin
The changes in peripheral blood Th17 and Treg ratios in Hashimoto’s thyroiditis are accompanied by differential PD-1/PD-L1 expression
Frontiers in Endocrinology
PD-1
PD-L1
Hashimoto’s thyroiditis
T helper 17 cells
T regulatory cells
title The changes in peripheral blood Th17 and Treg ratios in Hashimoto’s thyroiditis are accompanied by differential PD-1/PD-L1 expression
title_full The changes in peripheral blood Th17 and Treg ratios in Hashimoto’s thyroiditis are accompanied by differential PD-1/PD-L1 expression
title_fullStr The changes in peripheral blood Th17 and Treg ratios in Hashimoto’s thyroiditis are accompanied by differential PD-1/PD-L1 expression
title_full_unstemmed The changes in peripheral blood Th17 and Treg ratios in Hashimoto’s thyroiditis are accompanied by differential PD-1/PD-L1 expression
title_short The changes in peripheral blood Th17 and Treg ratios in Hashimoto’s thyroiditis are accompanied by differential PD-1/PD-L1 expression
title_sort changes in peripheral blood th17 and treg ratios in hashimoto s thyroiditis are accompanied by differential pd 1 pd l1 expression
topic PD-1
PD-L1
Hashimoto’s thyroiditis
T helper 17 cells
T regulatory cells
url https://www.frontiersin.org/articles/10.3389/fendo.2022.959477/full
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