Quantitative Analysis of Innate Lymphoid Cells in Patients with ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) is one of the principal causes of death in Mexico and worldwide. AMI triggers an acute inflammatory process that induces the activation of different populations of the innate immune system. Innate lymphoid cells (ILCs) are an innate immunity, highly pleiotropic population, which have been observed to participate in tissue repair and polarization of the adaptive immune response. OBJECTIVE: We aimed to analyze the levels of subsets of ILCs in patients with ST-segment elevation myocardial infarction (STEMI), immediately 3 and 6 months post-AMI, and analyze their correlation with clinical parameters. RESULTS: We evaluated 29 STEMI patients and 15 healthy controls and analyzed the different subsets of circulating ILCs, immediately 3 and 6 months post-AMI. We observed higher levels of circulating ILCs in STEMI patients compared to control subjects and a significant correlation between ILC levels and cardiac function. We also found increased production of the cytokines interleukin 5 (IL-5) and interleukin 17A (IL-17A), produced by ILC2 cells and by ILC3 cells, respectively, in the STEMI patients. CONCLUSION: This study shows new evidence of the role of ILCs in the pathophysiology of AMI and their possible involvement in the maintenance of cardiac function.

Regulatory T-cell frequency and function in acute myocardial infarction patients and its correlation with ventricular dysfunction.

A high percentage of patients with acute coronary syndrome develop heart failure due to the ischemic event. Regulatory T (Treg) cells are lymphocytes with suppressive capacity that control the immune response and include the conventional CD4+ CD25hi Foxp3+ cells and the CD4+ CD25var CD69+ LAP+ Foxp3- IL-10+ cells. No human follow-up studies focus on Treg cells' behavior after infarction and their possible relationship with ventricular function as a sign of postischemic cardiac remodeling. This study aimed to analyze, by flow cytometry, the circulating levels of CD69+ Treg cells and CD4+ CD25hi Foxp3+ cells, their IL-10+ production as well as their function in patients with acute myocardial infarction (AMI), and its possible relation with ventricular dysfunction. We found a significant difference in the percentage of CD4+ CD25hi Foxp3+ cells and IL-10+ MFI in patients with AMI at 72 hours compared with the healthy control group, and the levels of these cells were reduced 6 months post-AMI. Regarding the suppressive function of CD4+ CD25+ regulatory cells, they were dysfunctional at 3 and 6 months post-AMI. The frequency of CD69+ Treg cells was similar between patients with AMI at 72 hours postinfarction and the control groups. Moreover, the frequency of CD69+ Treg cells at 3 and 6 months postischemic event did not vary over time. Treg cells play a role in regulating inflammation after an AMI, and its function may be compromised in this pathology. This work is the first report to evaluate CD69+ Foxp3- Treg cells in AMI patients.

Differentiation of circulating monocytes into macrophages with metabolically activated phenotype regulates inflammation in dyslipidemia patients.

Macrophages are mediators of inflammation having an important role in the pathogenesis of cardiovascular diseases. Recently, a pro-inflammatory subpopulation, known as metabolically activated macrophages (MMe), has been described in conditions of obesity and metabolic syndrome where they are known to release cytokines that can promote insulin resistance. Dyslipidemia represents an important feature in metabolic syndrome and corresponds to one of the main modifiable risk factors for the development of cardiovascular diseases. Circulating monocytes can differentiate into macrophages under certain conditions. They correspond to a heterogeneous population, which include inflammatory and anti-inflammatory subsets; however, there is a wide spectrum of phenotypes. Therefore, we decided to investigate whether the metabolic activated monocyte (MoMe) subpopulation is already present under dyslipidemia conditions. Secondly, we assessed whether different levels of cholesterol and triglycerides play a role in the polarization towards the metabolic phenotype (MMe) of macrophages. Our results indicate that MoMe cells are found in both healthy and dyslipidemia patients, with cells displaying the following metabolic phenotype: CD14varCD36+ABCA1+PLIN2+. Furthermore, the percentages of CD14++CD68+CD80+ pro-inflammatory monocytes are higher in dyslipidemia than in healthy subjects. When analysing macrophage differentiation, we observed that MMe percentages were higher in the dyslipidemia group than in healthy subjects. These MMe have the ability to produce high levels of IL-6 and the anti-inflammatory cytokine IL-10. Furthermore, ABCA1 expression in MMe correlates with LDL serum levels. Our study highlights the dynamic contributions of metabolically activated macrophages in dyslipidemia, which may have a complex participation in low-grade inflammation due to their pro- and anti-inflammatory function.

Altered Phenotype of Circulating Dendritic Cells and Regulatory T Cells from Patients with Acute Myocarditis.

Dendritic cells (DCs) and regulatory T cells (Tregs) play an essential role in myocarditis. However, a particular DC phenotype in this disease has not been assessed. Herein, we aim to evaluate myeloid (mDCs) and plasmacytoid DC (pDC) phenotype, as well as Treg levels from myocarditis patients and healthy controls. Using multiparametric flow cytometry, we evaluated the levels of myeloid DCs (mDCs), plasmacytoid DCs (pDCs), and Tregs in peripheral blood from myocarditis patients (n = 16) and healthy volunteers (n = 16) and performed correlation analysis with clinical parameters through Sperman test. DCs from myocarditis patients showed a higher expression of costimulatory molecules while a diminished expression of the inhibitory receptors, ILT2 and ILT4. Even more, Treg cells from myocarditis patients displayed higher levels of FOXP3 compared to controls. Clinically, the increased levels of mDCs and their higher expression of costimulatory molecules correlate with a worse myocardial function, higher levels of acute phase reactants, and higher cardiac enzymes. This study shows an activating phenotype of circulating DCs from myocarditis patients. This proinflammatory status may contribute to the pathogenesis and immune deregulation in acute myocarditis.

Altered NK cell receptor repertoire and function of natural killer cells in patients with acute myocardial infarction: A three-month follow-up study.

NK cells are important in the onset of acute myocardial infarction (AMI) by their ability to secrete IFN-γ and other inflammatory cytokines. They also participate in regulating pathological cardiac remodeling after myocardial infarction. Mechanisms of regulation, however, are incompletely understood. Herein, the aim of this study is to explore the possible association between the expression pattern of different NK cell receptors (phenotype), as well as the cytotoxic function of NK cells from AMI patients with their myocardial function after three months follow-up. We analyzed the phenotype and function of both CD56dimCD16+ and CD56brightCD16- NK cells from twenty-one patients within the first 72 h after ST-elevation AMI and three-month follow-up, as well as fifteen healthy controls. Clinical characteristics and ventricular function determined by echocardiography were also evaluated. NK cells from AMI patients showed an activated phenotype, characterized by high TNF-α production and low percentages of the activating receptor NKG2D. Interestingly, AMI patients display higher levels of circulating IL-10+ NK cells. Three-month follow-up showed that NK cells exhibit a diminished cytotoxic function. These data show that NK cells may have a role mediating myocardial remodeling by regulating the inflammatory response, mainly by the production of IL-10. We also propose that NKG2D may have a role in the onset of the inflammatory response immediately after AMI. The precise regulation of NK cells function may represent an important step in recovery of myocardial function.