Altered Distribution of Circulating T Follicular Helper-Like Cell Subsets in Rheumatoid Arthritis Patients

Objective: Recent studies on follicular regulatory T (Tfr) and follicular helper T (Tfh) cells suggest that they may participate in the pathogenesis of rheumatoid arthritis (RA). Here, we examine Tfr-like and Tfh-like cells and their subsets in RA and assess the correlations between these subsets wi...

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Main Authors: Rui Su, Yanyan Wang, Fangyuan Hu, Baochen Li, Qiaoling Guo, Xinyu Zheng, Yue Liu, Chong Gao, Xiaofeng Li, Caihong Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2021.690100/full
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author Rui Su
Yanyan Wang
Fangyuan Hu
Baochen Li
Qiaoling Guo
Xinyu Zheng
Yue Liu
Chong Gao
Xiaofeng Li
Caihong Wang
author_facet Rui Su
Yanyan Wang
Fangyuan Hu
Baochen Li
Qiaoling Guo
Xinyu Zheng
Yue Liu
Chong Gao
Xiaofeng Li
Caihong Wang
author_sort Rui Su
collection DOAJ
description Objective: Recent studies on follicular regulatory T (Tfr) and follicular helper T (Tfh) cells suggest that they may participate in the pathogenesis of rheumatoid arthritis (RA). Here, we examine Tfr-like and Tfh-like cells and their subsets in RA and assess the correlations between these subsets with B cells and cytokines related to the pathogenesis of RA and their clinical significance.Methods: The study population consisted of 18 healthy controls and 47 RA patients (17 new onset, 57.00 ± 11.73 years; 30 treated RA patients, 57.56 ± 1.97 years). Disease activity scores in 28 joints were calculated. The positive rates of rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) were 82.9 and 89.4%, respectively. Cell subsets were analyzed using flow cytometry, and serum cytokine levels were measured using cytometric bead array.Results: Tfh-like and PD-1+ Tfh-like cells were elevated, and the distribution of Tfh-like cell subsets was altered with increased Tfh17-like and Tfh1/17-like cells in RA patients. The receiver operating characteristics curves for Tfh-like, Tfh17-like, Tfh1/17-like, and PD-1+ Tfh-like cells indicate improved RA diagnostic potential. RA patients had decreased regulatory T (Treg), Tfr-like, and memory Tfr-like (mTfr-like) cells and increased Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios. Tfh-like cells and their subsets, including Tfh1-like, Tfh2-like, Tfh1/17-like, and PD-1+ Tfh-like cells, were positively correlated with B cells. Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios were positively correlated with B cells in new-onset RA. Interleukin (IL)-2, IL-4, IL-17, interferon-γ, and tumor necrosis factor-α were positively correlated with Tfr-like and mTfr-like cells. IL-2 and IL-10 were positively correlated with Tfh-like and Tfh2-like cells. IL-4 was positively correlated with Tfh-like cells.Conclusions: Tfh-like and PD-1+ Tfh-like cells are increased, whereas Treg, Tfr-like, and mTfr-like cells are decreased in RA, leading to an imbalance in Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios. Tfh-like cells and a portion of their subsets as well as Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios are closely related to B cells. Dysfunction of cell subsets leads to abnormal levels of cytokines involved in the pathogenesis of RA. The altered distributions of Tfh-like cell subsets, especially Tfh1/17-like cells, represent potential therapeutic targets for treatment of RA.
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spelling doaj.art-7901a1826c2f4ddc9fa510f4ad3665f82022-12-21T18:22:07ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-07-01810.3389/fmed.2021.690100690100Altered Distribution of Circulating T Follicular Helper-Like Cell Subsets in Rheumatoid Arthritis PatientsRui Su0Yanyan Wang1Fangyuan Hu2Baochen Li3Qiaoling Guo4Xinyu Zheng5Yue Liu6Chong Gao7Xiaofeng Li8Caihong Wang9Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaPathology, Joint Program in Transfusion Medicine, Brigham and Women's Hospital/Children's Hospital Boston, Harvard Medical School, Boston, MA, United StatesDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaDepartment of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, ChinaObjective: Recent studies on follicular regulatory T (Tfr) and follicular helper T (Tfh) cells suggest that they may participate in the pathogenesis of rheumatoid arthritis (RA). Here, we examine Tfr-like and Tfh-like cells and their subsets in RA and assess the correlations between these subsets with B cells and cytokines related to the pathogenesis of RA and their clinical significance.Methods: The study population consisted of 18 healthy controls and 47 RA patients (17 new onset, 57.00 ± 11.73 years; 30 treated RA patients, 57.56 ± 1.97 years). Disease activity scores in 28 joints were calculated. The positive rates of rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) were 82.9 and 89.4%, respectively. Cell subsets were analyzed using flow cytometry, and serum cytokine levels were measured using cytometric bead array.Results: Tfh-like and PD-1+ Tfh-like cells were elevated, and the distribution of Tfh-like cell subsets was altered with increased Tfh17-like and Tfh1/17-like cells in RA patients. The receiver operating characteristics curves for Tfh-like, Tfh17-like, Tfh1/17-like, and PD-1+ Tfh-like cells indicate improved RA diagnostic potential. RA patients had decreased regulatory T (Treg), Tfr-like, and memory Tfr-like (mTfr-like) cells and increased Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios. Tfh-like cells and their subsets, including Tfh1-like, Tfh2-like, Tfh1/17-like, and PD-1+ Tfh-like cells, were positively correlated with B cells. Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios were positively correlated with B cells in new-onset RA. Interleukin (IL)-2, IL-4, IL-17, interferon-γ, and tumor necrosis factor-α were positively correlated with Tfr-like and mTfr-like cells. IL-2 and IL-10 were positively correlated with Tfh-like and Tfh2-like cells. IL-4 was positively correlated with Tfh-like cells.Conclusions: Tfh-like and PD-1+ Tfh-like cells are increased, whereas Treg, Tfr-like, and mTfr-like cells are decreased in RA, leading to an imbalance in Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios. Tfh-like cells and a portion of their subsets as well as Tfh-like/Treg, Tfh-like/Tfr-like, and Tfh-like/mTfr-like cell ratios are closely related to B cells. Dysfunction of cell subsets leads to abnormal levels of cytokines involved in the pathogenesis of RA. The altered distributions of Tfh-like cell subsets, especially Tfh1/17-like cells, represent potential therapeutic targets for treatment of RA.https://www.frontiersin.org/articles/10.3389/fmed.2021.690100/fullrheumatoid arthritisfollicular regulatory T cellsfollicular helper T cellsB cellssubsets
spellingShingle Rui Su
Yanyan Wang
Fangyuan Hu
Baochen Li
Qiaoling Guo
Xinyu Zheng
Yue Liu
Chong Gao
Xiaofeng Li
Caihong Wang
Altered Distribution of Circulating T Follicular Helper-Like Cell Subsets in Rheumatoid Arthritis Patients
Frontiers in Medicine
rheumatoid arthritis
follicular regulatory T cells
follicular helper T cells
B cells
subsets
title Altered Distribution of Circulating T Follicular Helper-Like Cell Subsets in Rheumatoid Arthritis Patients
title_full Altered Distribution of Circulating T Follicular Helper-Like Cell Subsets in Rheumatoid Arthritis Patients
title_fullStr Altered Distribution of Circulating T Follicular Helper-Like Cell Subsets in Rheumatoid Arthritis Patients
title_full_unstemmed Altered Distribution of Circulating T Follicular Helper-Like Cell Subsets in Rheumatoid Arthritis Patients
title_short Altered Distribution of Circulating T Follicular Helper-Like Cell Subsets in Rheumatoid Arthritis Patients
title_sort altered distribution of circulating t follicular helper like cell subsets in rheumatoid arthritis patients
topic rheumatoid arthritis
follicular regulatory T cells
follicular helper T cells
B cells
subsets
url https://www.frontiersin.org/articles/10.3389/fmed.2021.690100/full
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