Parisa Zafari1,2, Kheirollah Yari3,4, Shayan Mostafaei5, Nasrin Iranshahi1,2, Shirin Assar6, Adel Fekri1,2, Mahdi Taghadosi7. 1. a Student Research Committee, Medical school , Kermanshah University of Medical Sciences , Kermanshah , Iran. 2. b Faculty of Medicine , Kermanshah University of Medical Sciences , Kermanshah , Iran. 3. c Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran. 4. d Zagros Bioidea Laboratory , Razi University Incubator , Kermanshah , Iran. 5. e Rheumatology Research Center , Tehran University of Medical Sciences , Tehran , Iran. 6. f Clinical Research Development Center , Imam Reza Hospital, Kermanshah University of Medical Sciences , Kermanshah , Iran. 7. g Department of Immunology , Kermanshah University of Medical Sciences , Kermanshah , Iran.
Abstract
BACKGROUND: The control of auto-reactive cells is defective in rheumatoid arthritis (RA). Regulatory T (Treg) cells which play a key role in the modulation of immune responses have an impaired function in RA. Foxp3 is a master regulator of Treg cells which its expression is under the tight control of epigenetic mechanisms. In the current study, we analyzed the epigenetic modulation of the Foxp3 Treg-specific demethylated region (TSDR) and Helios gene expression to determine Treg cells alteration in RA patients. METHODS: We have recruited 20 newly diagnosed patients with RA and 41 healthy controls in our study. The measurement of Foxp3 and Helios gene expression was performed by the real-time PCR technique and the methylation level of TSDR was analyzed by bisulfite treatment and quantitative methylation-specific PCR (Q-MSP). RESULTS: We found that RA patients had significantly lower level of Foxp3 gene expression and TSDR demethylation compared to healthy subjects (P < 0.001 and P = 0.006, respectively). Inversely, the Helios gene expression was elevated significantly in RA patients group (P = 0.048). We also observed a significant correlation between Foxp3 and Helios gene expression (P = 0.016) as well as a significant correlation between FoxP3 expression and demethylation rate of TSDR (P = 0.010). CONCLUSION: Our results suggested that both epigenetic modifications and Helios gene expression may have important roles in the pathogenesis of RA through their effects on Foxp3 gene expression.
BACKGROUND: The control of auto-reactive cells is defective in rheumatoid arthritis (RA). Regulatory T (Treg) cells which play a key role in the modulation of immune responses have an impaired function in RA. Foxp3 is a master regulator of Treg cells which its expression is under the tight control of epigenetic mechanisms. In the current study, we analyzed the epigenetic modulation of the Foxp3 Treg-specific demethylated region (TSDR) and Helios gene expression to determine Treg cells alteration in RApatients. METHODS: We have recruited 20 newly diagnosed patients with RA and 41 healthy controls in our study. The measurement of Foxp3 and Helios gene expression was performed by the real-time PCR technique and the methylation level of TSDR was analyzed by bisulfite treatment and quantitative methylation-specific PCR (Q-MSP). RESULTS: We found that RApatients had significantly lower level of Foxp3 gene expression and TSDR demethylation compared to healthy subjects (P < 0.001 and P = 0.006, respectively). Inversely, the Helios gene expression was elevated significantly in RApatients group (P = 0.048). We also observed a significant correlation between Foxp3 and Helios gene expression (P = 0.016) as well as a significant correlation between FoxP3 expression and demethylation rate of TSDR (P = 0.010). CONCLUSION: Our results suggested that both epigenetic modifications and Helios gene expression may have important roles in the pathogenesis of RA through their effects on Foxp3 gene expression.
Authors: M-H Haddadi; B Negahdari; E Hajizadeh-Saffar; M Khosravi-Maharlooei; M Basiri; H Dabiri; H Baharvand Journal: Clin Exp Immunol Date: 2020-06-08 Impact factor: 4.330
Authors: Agnieszka Paradowska-Gorycka; Anna Wajda; Katarzyna Romanowska-Próchnicka; Ewa Walczuk; Ewa Kuca-Warnawin; Tomasz Kmiolek; Barbara Stypinska; Ewa Rzeszotarska; Dominik Majewski; Pawel Piotr Jagodzinski; Andrzej Pawlik Journal: Front Immunol Date: 2020-12-11 Impact factor: 7.561