Increased proportions of functionally impaired regulatory T cell subsets in systemic sclerosis

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Emese UgorTímea Berki

Abstract

Treg abnormalities have been implicated in the pathogenesis of systemic sclerosis (SSc). Treg subpopulations and their cytokines, IL-10 and TGF-β in the peripheral blood of early stage SSc patients were investigated. We hypothesized that epigenetically regulated methylation of the FOXP3 promoter and enhancer regions are altered in Tregs of SSc patients, which might be involved in the T cell imbalance. CD4+CD25+Foxp3+CD127- Treg cells were significantly elevated in patients with diffuse cutaneous SSc and in patients with anti-Scl-70/RNA-Pol-III autoantibody positivity and with lung fibrosis. Increased CD62L+ Treg cells were present in all SSc subgroups. The production of immunosuppressive cytokines by both CD127- and CD62L+ Tregs was diminished. We observed reduced methylation of Treg specific FOXP3 enhancer regions, and elevated FOXP3 gene expression in active SSc cases with negative correlation in the frequency of CD62L+IL-10+ Tregs. Our data indicate an inappropriate distribution and cytokine production of Treg cells in early form SSc.

References

Jan 5, 2016·Cytokine & Growth Factor Reviews·Mengguo LiuMing Li

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Citations

Sep 21, 2018·Current Opinion in Rheumatology·Patrizia Fuschiotti
Mar 14, 2019·International Immunology·Lokesh A Kalekar, Michael D Rosenblum
Oct 31, 2018·Frontiers in Immunology·Camelia FrantzYannick Allanore
Jul 28, 2020·Rheumatology International·Bohdana DoskaliukOlena Zimba
Apr 7, 2019·Seminars in Immunopathology·Lisa GöschlMichael Bonelli
Dec 10, 2019·Current Rheumatology Reports·Pei-Suen Tsou
Jan 8, 2021·Arthritis Research & Therapy·David A FoxDinesh Khanna
Jan 16, 2021·Clinical Reviews in Allergy & Immunology·Ming ZhaoQianjin Lu
Jan 22, 2021·Autoimmunity Reviews·Zhussipbek MukhatayevI Caroline Le Poole
Feb 27, 2021·International Journal of Immunopathology and Pharmacology·Xinjuan LiuXiaofeng Zeng
Jul 24, 2021·The Journal of Investigative Dermatology·Jörg Christoph Prinz

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