Obesity influences T CD4 lymphocytes subsets profiles in children and adolescent's immune response.

PURPOSE: Evidence shows that CD4+ T cells are altered in obesity and play a significant role in the systemic inflammation occurring in adults with the disease. Since the profile of these cells is poorly understood in the pediatric population, the present study aims to investigate the profile of CD4+ T lymphocytes and the plasma levels of cytokines in this population. METHODS: Using flow cytometry, we compared the expression profile of lymphocyte markers, master transcription factors, cytokines and molecules involved in the regulation of the immune response in CD4+ T cells from children and adolescents with obesity (OB group, n=20) to those with eutrophy (EU group, n=16). Plasma levels of cytokines in both groups were determined by CBA. RESULTS: The OB group presents a lower frequency of CD3+ T cells, as well as a decreased frequency of CD4+ T cells expressing CD28, IL-4, and FOXP3, but an increased frequency of CD4+IL-17A+ cells compared to the EU group. The frequency of CD28 is increased in Th2 and Treg cells in the OB group, while CTLA-4 is decreased in all subpopulations compared to the EU group. Furthermore, Th2, Th17 and Treg profiles can differentiate the EU and OB groups. IL-10 plasma levels are reduced in the OB group and negatively correlated with adiposity and inflammatory parameters. CONCLUSION: CD4+ T cells have an altered pattern of expression in children and adolescents with obesity, contributing to the inflammatory state and clinical characteristics of these patients.

COVID-19, obesity, and immune response 2 years after the pandemic: A timeline of scientific advances.

In the 2 years since the COVID-19 pandemic was officially declared, science has made considerable strides in understanding the disease's pathophysiology, pharmacological treatments, immune response, and vaccination, but there is still much room for further advances, especially in comprehending its relationship with obesity. Science has not yet described the mechanisms that explain how obesity is directly associated with a poor prognosis. This paper gathers all published studies over the past 2 years that have described immune response, obesity, and COVID-19, a historical and chronological record for researchers and the general public alike. In summary, these studies describe how the cytokine/adipokine levels and inflammatory markers, such as the C-reactive protein, are associated with a higher body mass index in COVID-19-positive patients, suggesting that the inflammatory background and immune dysregulation in individuals with obesity may be expressed in the results and that adiposity may influence the immune response. The timeline presented here is a compilation of the results of 2 years of scientific inquiry, describing how the science has progressed, the principal findings, and the challenges ahead regarding SARS-CoV-2, COVID-19, and emerging variants, especially in patients with obesity.

Modulation of Regulatory T Cells Activity by Distinct CD80 and CD86 Interactions With CD28/CTLA-4 in Chagas Cardiomyopathy.

Chagas cardiomyopathy is the symptomatic cardiac clinical form (CARD) of the chronic phase of Chagas disease caused by Trypanosoma cruzi infection. It was described as the most fibrosing cardiomyopathies, affecting approximately 30% of patients during the chronic phase. Other less frequent symptomatic clinical forms have also been described. However, most patients who progress to the chronic form develop the indeterminate clinical form (IND), may remain asymptomatic for life, or develop some cardiac damage. Some mechanisms involved in the etiology of the clinical forms of Chagas disease have been investigated. To characterize the contribution of CD80 and CD86 co-stimulatory molecules in the activation of different CD4+ (Th1, Th2, Th17, and Treg) and CD8+ T lymphocyte subsets, we used blocking antibodies for CD80 and CD86 receptors of peripheral blood mononuclear cells (PBMC) in cultures with T. cruzi antigens from non-infected (NI), IND, and CARD individuals. We demonstrated a higher frequency of CD8+ CD25+ T lymphocytes and CD8+ Treg cells after anti-CD80 antibody blockade only in the CARD group. In contrast, a lower frequency of CD4+ Treg lymphocytes after anti-CD86 antibody blockade was found only in IND patients. A higher frequency of CD4+ Treg CD28+ lymphocytes, as well as an association between CD4+ Treg lymphocytes and CD28+ expression on CD4+ Treg cells in the CARD group, but not in IND patients, and once again only after anti-CD80 antibody blockade, was observed. We proposed that Treg cells from IND patients could be activated via CD86-CTLA-4 interaction, leading to modulation of the immune response only in asymptomatic patients with Chagas disease, while CD80 may be involved in the proliferation control of T CD8+ lymphocytes, as also in the modulation of regulatory cell activation via CD28 receptor. For the first time, our data highlight the role of CD80 in modulation of Treg lymphocytes activation in patients with CARD, highlighting a key molecule in the development of Chagas cardiomyopathy.

Crosstalk Between Plasma Cytokines, Inflammation, and Liver Damage as a New Strategy to Monitoring NAFLD Progression.

Cytokines are involved in the immunopathogenesis of nonalcoholic fatty liver disease (NAFLD), but the relationship between them and clinical parameters of NAFLD progression is still unknown. Using flow cytometry, we evaluated the plasma levels of IL-1ß, IL-6, IL-12, TNF and IL-10 and their association with clinical and biochemical parameters of liver function during simple steatosis (NAFL) and nonalcoholic steatohepatitis (NASH) in biopsy-proven patients. The NASH patients showed higher levels of IL-6 associated with a lower IL-10/IL-6 ratio. Besides heatmaps were similar in the NAFL and NASH groups, the same did not occur in signature curves, the NASH patients were high producers to IL-12 and IL-6 while the NAFL patients were not high producers of any cytokines evaluated. Integrative biomarker network analysis revealed that cytokines are differently correlated with clinical parameters, while IL-12, IL-10 presented moderate and negative correlations with glycemic and lipid profile in the NAFL group. The NASH group IL-12 and TNF revealed stronger and positive correlations with transient elastography parameters and NAFLD liver fibrosis score. These data suggest that IL-6 and IL-10 might act in chronic inflammation and insulin resistance whereas IL-12 and TNF may be involved in promoting liver damage and NAFLD progression. Plasma concentration analysis of these molecules and their association with clinical parameters can be used as new biomarkers to monitoring NAFLD progression and to reflect NASH development.