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Cited by 14Rheumatoid Arthritis Research and TherapiesT-cell and B-cell ImmunologyPsoriasis: Treatment and Pathogenesis

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The proportion and phenotypic changes of CD4+CD25-Foxp3+ T cells in patients with untreated rheumatoid arthritis

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Ju, Bomiao, Zhu, Li, Wang, Jing, Zheng, Jian, Hao, Zhiming, Luo, Jing, Zhang, Jing, Hu, Nan, An, Qi, Feng, Xiuyuan, Huo, Yongwei, He, Lan·2022·BMC Immunology
DOI 10.1186/s12865-022-00517-0PMC PMC9446710
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Abstract

Objective: CD4+CD25+Foxp3+ regulatory T (Treg) cell-mediated immunosuppression is an essential mechanism of rheumatoid arthritis (RA). However, little is known regarding the specific role of CD4+CD25−Foxp3+ Treg cells in RA. This study aimed to investigate the frequency of circulating CD4+CD25−Foxp3+ Treg cells and their role in RA. Methods: Sixty-one untreated RA patients and 40 healthy controls (HCs) were enrolled in this study. The proportion of CD4+CD25−Foxp3+ T cells and CD4+CD25+Foxp3+ Tregs; the levels of CTLA4, GITR, Helios, and ICOS; and the production of IL-17A, IFN-γ, and IL-10 were assessed by flow cytometry. The correlation of CD4+CD25–Foxp3+ T cells and CD4+CD25+Foxp3+ Tregs with the clinical indicators was conducted by Spearman correlation analysis. Results: The proportion of CD4+CD25–Foxp3+ T cells was elevated in RA and positively correlated with disease activity. CD4+CD25–Foxp3+ T cells expressed less Helios and produced more IFN-γ than conventional Tregs in RA. Additionally, the proportion of CD4+CD25–Foxp3+ T cells was positively correlated with DAS28 score, IgG titer, and anti-CCP titer. Conclusions: These data indicate that CD4+CD25−Foxp3+ T cells in RA exhibit several different functional properties from conventional Tregs and are correlated with RA disease activity.

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Fig. 1 Elevated proportions of CD4+CD25-Foxp3+ T cells and CD4+CD25+Foxp3+ Treg cells in RA: a representative flow cytometry plots. b The proportion of CD4+CD25−Foxp3+ T cells in the PB of HCs, total untreated RA patients, inactive RA patients, and active RA patients. c The proportion of CD4+CD25+Foxp3+ Treg cells in the PB of HCs, total untreated RA patients, inactive RA patients and active RA patients. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001. HCs, healthy controls; RA, rheumatoid arthritis.
Fig. 1 Elevated proportions of CD4+CD25-Foxp3+ T cells and CD4+CD25+Foxp3+ Treg cells in RA: a representative flow cytometry plots. b The proportion of CD4+CD25−Foxp3+ T cells in the PB of HCs, total untreated RA patients, inactive RA patients, and active RA patients. c The proportion of CD4+CD25+Foxp3+ Treg cells in the PB of HCs, total untreated RA patients, inactive RA patients and active RA patients. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001. HCs, healthy controls; RA, rheumatoid arthritis.CC BY · PubMed Central
Fig. 2 The correlation between the proportions of CD4+CD25−Foxp3+ T cells and CD4+CD25+Foxp3+ Treg cells and clinical variables. a, b The Spearman rank test was used to analyse the correlation between the CD4+CD25−Foxp3+ T cells or CD4+CD25+Foxp3+ Treg cells and DAS28-ESR, IgG titer, IgM titer, and anti-CCP titer.
Fig. 2 The correlation between the proportions of CD4+CD25−Foxp3+ T cells and CD4+CD25+Foxp3+ Treg cells and clinical variables. a, b The Spearman rank test was used to analyse the correlation between the CD4+CD25−Foxp3+ T cells or CD4+CD25+Foxp3+ Treg cells and DAS28-ESR, IgG titer, IgM titer, and anti-CCP titer.CC BY · PubMed Central

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References 22 · Cited by 14

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Metadata

Authors
Ju, B., Zhu, L., Wang, J., Zheng, J., Hao, Z., Luo, J., Zhang, J., Hu, N., An, Q., Feng, X., Huo, Y., & He, L.
Affiliations
  • First Affiliated Hospital of Xi'an Jiaotong University (CN)
  • Xi'an Jiaotong University (CN)
Corresponding author
He, Lan
ORCID
Venue
BMC Immunology
Publisher
Springer Science and Business Media LLC
Published
2022-09-06
Volume
23
Issue
1
Pages
41-41
ISSN
1471-2172 (ISSN-L)
DOI
10.1186/s12865-022-00517-0
PMC
PMC9446710
OpenAlex
W4294676823
Cited by
14
References
22
Citations by year
2026: 2 · 2025: 2 · 2024: 6 · 2023: 4
FWCI
2.18
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • the Natural Science Basis Research Plan in Shaanxi Province of China (Program No. 2022JQ-958)
  • the institutional foundation of the First Affiliated Hospital of Xi'an Jiaotong University (2015YK10, 2018 MS-16)
Topics
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
rheumatoid arthritis, regulatory T cells, Helios, interferon-gamma, disease activity, DAS28, anti-CCP antibodies, CTLA-4, GITR, ICOS, untreated rheumatoid arthritis
MeSH terms
Arthritis, Rheumatoid, Humans, Immune Tolerance, Interferon-gamma, T-Lymphocytes, Regulatory, Forkhead Transcription Factors, Interleukin-2 Receptor alpha Subunit

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CoChat. (2026). Citation check: The proportion and phenotypic changes of CD4+CD25-Foxp3+ T cells in patients with untreated rheumatoid arthritis. https://app.cochat.ai/papers/10.1186/s12865-022-00517-0
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Ju, B., Zhu, L., Wang, J., Zheng, J., Hao, Z., Luo, J., Zhang, J., Hu, N., An, Q., Feng, X., Huo, Y., & He, L. (2022). The proportion and phenotypic changes of CD4+CD25-Foxp3+ T cells in patients with untreated rheumatoid arthritis. BMC Immunology. https://doi.org/10.1186/s12865-022-00517-0