scholarly journals IFN Regulatory Factor-1 Modulates the Function of Dendritic Cells in Patients with Acute Coronary Syndrome

2015 ◽  
Vol 36 (2) ◽  
pp. 599-610 ◽  
Author(s):  
Min Guo ◽  
Rui Yan ◽  
Caixia Wang ◽  
Hongtao Shi ◽  
Meng Sun ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Coronary Syndrome ◽  
Dendritic Cells ◽  
Mapk Pathway ◽  
Human Monocyte ◽  
Regulatory Factor ◽  
Coronary Syndrome ◽  
Artery Disease ◽  
And Function

Background: Atherosclerosis is widely recognized as a complex inflammatory disease involving pathogenic immune response of T cells and antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages. Accumulating evidence has revealed that mature DCs play critical roles in the differentiation of effector T cells into CD4+ T cells, which effectively participate in the onset of acute coronary syndrome (ACS). IFN regulatory factor (IRF)-1 has been shown to be involved in various immune processes. The role of IRF-1 in DCs in the pathogenesis of ACS has not been investigated. Methods and Results: We examined the relative mRNA and protein expression of IRF-1 in human monocyte-derived DCs in patients with coronary artery disease (CAD). The overexpression or silencing of IRF-1 expression in DCs in patients with ACS was performed to explore the possible role of IRF-1 in the maturation and function of DCs involved in ACS. The results showed that the relative expression of IRF-1 in DCs is obviously increased in patients with ACS. The overexpression or silencing of IRF-1 expression could effectively promote or attenuate the maturation and function of DCs. In addition, we revealed that the MAPK pathway (phosphorylation of JNK, p38 and ERK1/2) might be downstream of IRF-1 signalling pathway in activation of circulating DCs in ACS patients. Conclusion: The present data demonstrate that IRF-1 could effectively promote the immune maturation and function of DCs in ACS patients.

scholarly journals Inhibition of O-GlcNAc Transferase Alters the Differentiation and Maturation Process of Human Monocyte Derived Dendritic Cells

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3312
Author(s):  
Matjaž Weiss ◽  
Marko Anderluh ◽  
Martina Gobec
Keyword(s):  
Dendritic Cells ◽  
Posttranslational Modification ◽  
Human Monocyte ◽  
T Cell Differentiation ◽  
Maturation Process ◽  
Hla Dr ◽  
Glcnac Transferase ◽  
And Function

The O-GlcNAcylation is a posttranslational modification of proteins regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase. These enzymes regulate the development, proliferation and function of cells, including the immune cells. Herein, we focused on the role of O-GlcNAcylation in human monocyte derived dendritic cells (moDCs). Our study suggests that inhibition of OGT modulates AKT and MEK/ERK pathways in moDCs. Changes were also observed in the expression levels of relevant surface markers, where reduced expression of CD80 and DC-SIGN, and increased expression of CD14, CD86 and HLA-DR occurred. We also noticed decreased IL-10 and increased IL-6 production, along with diminished endocytotic capacity of the cells, indicating that inhibition of O-GlcNAcylation hampers the transition of monocytes into immature DCs. Furthermore, the inhibition of OGT altered the maturation process of immature moDCs, since a CD14medDC-SIGNlowHLA-DRmedCD80lowCD86high profile was noticed when OGT inhibitor, OSMI-1, was present. To evaluate DCs ability to influence T cell differentiation and polarization, we co-cultured these cells. Surprisingly, the observed phenotypic changes of mature moDCs generated in the presence of OSMI-1 led to an increased proliferation of allogeneic T cells, while their polarization was not affected. Taken together, we confirm that shifting the O-GlcNAcylation status due to OGT inhibition alters the differentiation and function of moDCs in in vitro conditions.

Abstract 4008: PSGL-1-Expressing CD4 T Cells are Enriched in Culprit Coronary Artery Lesion of Acute Coronary Syndrome

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Keiko Gomita ◽  
Kayoko Sato ◽  
Kazutaka Kitamura ◽  
Nobuhisa Hagiwara
Keyword(s):  
T Cells ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Adhesion Molecules ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Coronary Artery Lesion ◽  
Plaque Instability ◽  
Coronary Syndrome

Background: Recently, several evidences on the crucial role of adhesion molecules in the development of atherosclerosis and plaque instability have been reported. While expression of VCAM-1, ICAM-1 and L-selectin has been consistently observed in atherosclerotic plaques it is still uncertain how adhesion molecules on T cells contribute to the incidence of acute coronary syndrome (ACS). In this study, we examined whether adhesion molecules on T cells in ACS have a significant role in the plaque stability and prone to cause ACS. Methods and Results: Fresh CD4 T cells were isolated from the peripheral blood of 76 ACS patients (AMI=35, UAP=41) and 74 age-matched controls (NC). CD69, an activation marker of T cells, was strongly expressed on CD4 T cells from ACS than from NC by FACS (P<0.0001). CD4 T cells from ACS highly expressed p-selectin glycoprotein ligand-1 (PSGL-1) and integrin β (CD18), but not L-selectin by FACS (P < 0.03, P < 0.01, n.s., respectively). Soluble PSGL-1 (sPSGL-1) levels in plasma were lower in ACS patients than in NC (P=0.0001), which correlated negatively with the PSGL-1 expression on CD4 T cells (R=0.405, P<0.02). We further investigated the thrombus-aspirating device samples (n=14) and fresh CD4 T cells derived from both the coronary artery and peripheral blood from the each same patient with ACS. CD4 T cells from the coronary artery strongly expressed PSGL-1 (P<0.002), but not integrin β (CD18) and L-selectin by FACS. Finally, PSGL-1 was expressed on T cells, but not on CD68 positive macrophage, MPO positive neutrophil, or CD41 positive platelets in the thrombus-aspirating device samples. Conclusions: From these results, we demonstrated that PSGL-1-expressing CD4 T cells are enriched in the culprit coronary artery lesion of ACS, contributing to the acceleration of plaque instability and occurrence of ACS.

scholarly journals MicroRNAs as Regulators and Biomarkers of Platelet Function and Activity in Coronary Artery Disease

2019 ◽  
Vol 119 (10) ◽  
pp. 1563-1572 ◽  
Author(s):  
Stefan Stojkovic ◽  
Anne Yaël Nossent ◽  
Paul Haller ◽  
Bernhard Jäger ◽  
Kris G. Vargas ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Treatment Response ◽  
Platelet Function ◽  
Ribonucleic Acids ◽  
Coronary Syndrome ◽  
Artery Disease ◽  
Response Biomarkers

AbstractMicroribonucleic acids (miRs) are small, noncoding ribonucleic acids (RNAs), which play an important role in the regulation of platelet function and activity. Several studies proposed a mechanistic role of platelet-related miRs in the pathophysiology of coronary artery disease (CAD) and atherothrombosis. Circulating, platelet-related miRs have been proposed as diagnostic, prognostic, as well as treatment response biomarkers in CAD and acute coronary syndrome (ACS). In this review, we summarize recent studies on the role of platelet-related miRs in the regulation of platelet function and activity. Furthermore, we review the studies investigating the role of platelet-related miRs as biomarkers in patients with CAD and ACS.

scholarly journals Monoclonal antibodies to LFA-1 and to CD4 inhibit the mixed leukocyte reaction after the antigen-dependent clustering of dendritic cells and T lymphocytes.

1987 ◽  
Vol 165 (5) ◽  
pp. 1403-1417 ◽  
Author(s):  
K Inaba ◽  
R M Steinman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cell Mediated Immunity ◽  
Lymphocyte Function ◽  
Mixed Leukocyte Reaction ◽  
Binding Assays ◽  
Lymphocyte Blastogenesis ◽  
And Function

T cell proliferation in response to many stimuli is known to occur in discrete clusters of dendritic cells (DC) and CD4+ helper lymphocytes. The role of lymphocyte function-associated antigen (LFA-1) and CD4 in the formation and function of these clusters has been evaluated in the mixed leukocyte reaction (MLR). By day 1 of the control MLR, most of the DC and responsive T cells are associated in discrete aggregates. Addition of anti-LFA-1 and CD4 reagents does not block DC-T aggregation but reduces the subsequent proliferative response by 80-90%. Anti-LFA-1 disassembles newly formed DC-T cell aggregates, whereas anti-CD4 inhibits blastogenesis without disrupting the cluster. Binding of DC to sensitized, antigen-specific CD4+ cells has been studied using lymphoblasts isolated at day 4 of the MLR. It has been shown previously that greater than 80% blasts rebind to DC in an antigen-specific fashion in rapid (10 min) binding assays. Antigen-dependent DC-T binding is blocked by anti-Ia but not by mAb to LFA-1 or CD4. However, the bound anti-CD4-coated lymphocytes are unable to release IL-2. Anti-LFA-1-coated T cells release IL-2 but are easily disaggregated after binding to DC. These findings lead to two conclusions. LFA-1 and CD4 are not involved in the initial steps whereby DC bind to T cells but exert an independent and subsequent role. LFA-1 acts to stabilize the DC-T cluster, while CD4 contributes to lymphocyte blastogenesis and IL-2 release. Because DC but not other presenting cells cluster unprimed lymphocytes, it seems likely that an antigen-independent mechanism distinct from LFA-1 and CD4 mediates aggregate formation at the onset of cell-mediated immunity.

scholarly journals The role of nutritional indexes in predicting coronary artery disease severity in acute coronary syndrome

2021 ◽  
Vol 63 (2) ◽  
pp. 147-152
Author(s):  
Hatice Tolunay ◽  
Suat Görmel ◽  
Serkan Asil ◽  
Salim Yaşar ◽  
Erkan Yıldırım ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Disease Severity ◽  
Coronary Syndrome ◽  
Coronary Artery Disease Severity ◽  
Artery Disease

scholarly journals Interleukin-7 and interleukin-15 drive CD4+CD28null T lymphocyte expansion and function in patients with acute coronary syndrome

2020 ◽  
Author(s):  
Jessica Bullenkamp ◽  
Veronica Mengoni ◽  
Satdip Kaur ◽  
Ismita Chhetri ◽  
Paraskevi Dimou ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Coronary Syndrome ◽  
T Cell ◽  
T Lymphocyte ◽  
Cell Expansion ◽  
Cell Subset ◽  
Coronary Syndrome ◽  
Tnf Α ◽  
T Cell Expansion ◽  
And Function

Abstract Aims Inflammation has important roles in atherosclerosis. CD4+CD28null (CD28null) T cells are a specialized T lymphocyte subset that produce inflammatory cytokines and cytotoxic molecules. CD28null T cells expand preferentially in patients with acute coronary syndrome (ACS) rather than stable angina and are barely detectable in healthy subjects. Importantly, ACS patients with CD28null T-cell expansion have increased risk for recurrent acute coronary events and poor prognosis, compared to ACS patients in whom this cell subset does not expand. The mechanisms regulating CD28null T-cell expansion in ACS remain elusive. We therefore investigated the role of cytokines in CD28null T-cell expansion in ACS. Methods and results High-purity sorted CD4+ T cells from ACS patients were treated with a panel of cytokines (TNF-α, IL-1β, IL-6, IL-7, and IL-15), and effects on the number, phenotype, and function of CD28null T cells were analysed and compared to the control counterpart CD28+ T-cell subset. IL-7- and IL-15-induced expansion of CD28null T cells from ACS patients, while inflammatory cytokines TNF-α, IL-1β, and IL-6 did not. The mechanisms underlying CD28null T-cell expansion by IL-7/IL-15 were preferential activation and proliferation of CD28null T cells compared to control CD28+ T cells. Additionally, IL-7/IL-15 markedly augmented CD28null T-cell cytotoxic function and interferon-γ production. Further mechanistic analyses revealed differences in baseline expression of component chains of IL-7/IL-15 receptors (CD127 and CD122) and increased baseline STAT5 phosphorylation in CD28null T cells from ACS patients compared to the control CD28+ T-cell subset. Notably, we demonstrate that CD28null T-cell expansion was significantly inhibited by Tofacitinib, a selective JAK1/JAK3 inhibitor that blocks IL-7/IL-15 signalling. Conclusion Our novel data show that IL-7 and IL-15 drive the expansion and function of CD28null T cells from ACS patients suggesting that IL-7/IL-15 blockade may prevent expansion of these cells and improve patient outcomes.

scholarly journals Role of Diabetic Dyslipidemia on Coronary Atherosclerotic Severity in Acute Coronary Syndrome

2017 ◽  
Vol 31 (2) ◽  
pp. 65-69
Author(s):  
Golam Mahfuz Rabbani ◽  
Afzalur Rahman ◽  
Anisur Rahman Khan ◽  
Nur Hossain ◽  
Muhammad Badrul Alam ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Analytical Study ◽  
Cross Sectional ◽  
High Tc ◽  
Medical College ◽  
Coronary Syndrome ◽  
Low Hdl ◽  
Artery Disease ◽  
Age Range

Aims: To evaluate the association of coronary atherosclerotic severity in diabetic dyslipidemic patients of acute coronary syndrome.Methods: This was a cross sectional comparative analytical study, done in the Department of Cardiology, Sir Salimullah Medical College Mitford Hospital and Ibrahim Cardiac Hospital & Research Institute, Dhaka, during September 2009 to August 2010.Results: Most of the patients (57.5%) were in the age range of 40-70 years. Atherosclerotic severity in diabetic ACS patients was significantly higher with low HDL, high TC/HDL and high LDL/HDL ratio. Low HDL, high TC/HDL and high LDL/HDL ratio are indicators of the extent and severity of coronary artery disease. More frequent dyslipidemia in diabetic ACS patients were low HDL and it was about 54%.Conclusion: Atherosclerotic severity in diabetic acute coronary syndrome patients was significantly more in dyslipidemic group than non dyslipidemic group.Bangladesh Heart Journal 2016; 31(2) : 65-69

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