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Heme Oxygenase-1 Restores Impaired GARPCD4+CD25+ Regulatory T Cells from Patients with Acute Coronary Syndrome by Upregulating LAP and GARP Expression on Activated T Lymphocytes.
- Source :
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Cellular Physiology & Biochemistry (Karger AG) . Jan2015, Vol. 35 Issue 2, p553-570. 18p. - Publication Year :
- 2015
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Abstract
- Background: Accumulating evidence shows that the pathological autoreactive immune response is responsible for plaque rupture and the subsequent onset of acute coronary syndrome (ACS). Naturally occurring CD4+CD25+regulatory T cells (nTregs) are indispensable in suppressing the pathological autoreactive immune response and maintaining immune homeostasis. However, the number and the suppressive function of glycoprotein-A repetitions predominant (GARP) + CD4+ CD25+ activated nTregs were impaired in patients with ACS. Recent evidence suggests that heme oxygenase-1 (HO-1) can regulate the adaptive immune response by promoting the expression of Foxp3. We therefore hypothesized that HO-1 may enhance the function of GARP+ CD4+ CD25+Tregs in patients with ACS and thus regulate immune imbalance. Methods: T lymphocytes were isolated from healthy volunteers (control, n=30) and patients with stable angina (SA, n=40) or ACS (n=51). Half of these cells were treated with an HO-1 inducer (hemin) for 48 h, and the other half were incubated with complete RPMI-1640 medium. The frequencies of T-helper 1 (Th1), Th2, Th17 and latency-associated peptide (LAP) +CD4+ T cells and the expression of Foxp3 and GARP by CD4+CD25+T cells were then assessed by measuring flow cytometry after stimulation in vitro. The suppressive function of activated Tregs was measured by thymidine uptake. The levels of transforming growth factor-1 (TGF-β1) in the plasma were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of the genes encoding these proteins were analyzed by real-time polymerase chain reaction. Results: Patients with ACS exhibited an impaired number and suppressive function of GARP+ CD4+ CD25+Tregs and a mixed Th1/Th17-dominant T cell response when compared with the SA and control groups. The expression of LAP in T cells was also lower in patients with ACS compared to patients with SA and the control individuals. Treatment with an HO-1 inducer enhanced the biological activity of GARP+ CD4+ CD25+Tregs and resulted in increased expression of LAP and GARP by activated T cells. Conclusions: The reduced number and impaired suppressive function of GARP+ CD4+ CD25+Tregs result in excess effector T cell proliferation, leading to plaque instability and the onset of ACS. HO-1 can effectively restore impaired GARP+ CD4+ CD25+Tregs from patients with ACS by promoting LAP and GARP expression on activated T cells. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10158987
- Volume :
- 35
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Cellular Physiology & Biochemistry (Karger AG)
- Publication Type :
- Academic Journal
- Accession number :
- 100713977
- Full Text :
- https://doi.org/10.1159/000369719