Th2/Th1 cytokine imbalance is associated with higher COVID-19 risk mortality
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ABSTRACT:
PROVIDER: PRJNA738876 | ENA |
REPOSITORIES: ENA
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Project description:In this study we profiled 288 new serum proteomics samples measured at admission from patients hospitalized within the Mount Sinai Health System with positive SARS-CoV-2 infection. We first computed Th1 and Th2 pathway enrichment scores by gene set variation analysis and then compared the differences in Th2 and Th1 pathway scores between patients that died compared to those that survived.
2022-06-16 | GSE178399 | GEO
Project description:A major component of COVID-19 severe respiratory syndrome is the patient's immune response to the SARS-CoV-2 virus and the consequential multi-organ inflammatory response. Several studies suggested a potential role of CD4+ T cells in COVID-19 severe respiratory syndrome. We first hypothesized that there is a type 2 helper (Th2)/type 1 helper (Th1) imbalance in older age, male, asthma, smokers, and high ACE2 expression phenotype in the airway of non-infected patients. Next, we hypothesized that a Th2/Th1 imbalance may predict higher mortality in COVID-19 infected hospitalized patients with and without patient reported current asthma. We first analyzed publicly available gene expression from the sputum of 118 moderate-to-severe asthma patients and 21 healthy controls, and from nasal epithelium of 26 healthy current smokers and 21 healthy never smokers. Secondly, we profiled 288 new serum proteomics samples measured at admission from patients hospitalized within the Mount Sinai Health System with positive SARS-CoV-2 infection. We first computed Th1 and Th2 pathway enrichment scores by gene set variation analysis and then compared the differences in Th2 and Th1 pathway scores between patients that died compared to those that survived, by linear regression. The level of Th2/Th1 imbalance, as determined by the enrichment score, was associated with age, sex, and ACE2 expression in sputum, and with active smoking status in nasal epithelium (p < 0.05). Th2/Th1 imbalance at hospital admission in sera of patients was not significantly associated with death from COVID-19 (p = 0.11), unless evaluated in the asthmatic strata (p = 0.01). Using a similar approach we also observed a higher Th17/Th1 cytokine imbalance in all deceased patients compared to those that survived (p < 0.001), as well as in the asthmatic strata only (p < 0.01). Th2/Th1 imbalance is higher in the sera of asthma patients at admission that do not survive COVID-19, suggesting that the Th2/Th1 interplay may affect patient outcomes in SARS-CoV2 infection. In addition, we report that Th17/Th1 imbalance is increased in all patients that die of COVID-19.
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Project description:This is a mathematical model describing the imbalance between T helper (Th1/Th2) cell types in melanome patients, together with its regulation via IL-12 treatment. The model focuses on the interactions between the two T helper cell types as mediated by their respective key cytokines, interferon gamma and IL-10.
2024-09-02 | BIOMD0000000881 | BioModels
Project description:T helper cell subsets have unique calcium (Ca2+) signals when activated with identical stimuli. The regulation of these Ca2+ signals and their correlation to the biological function of each T cell subset remains unclear. Trpm4 is a Ca2+-activated cation channel that we found is expressed at higher levels in Th2 cells compared to Th1 cells. Inhibition of Trpm4 expression increased Ca2+ influx and oscillatory levels in Th2 cells and decreased influx and oscillations in Th1 cells. This inhibition of Trpm4 expression also significantly altered T cell cytokine production and motility. Our experiments revealed that decreasing Trpm4 levels divergently regulates nuclear localization of NFAT. Consistent with this, gene profiling did not show Trpm4 dependent transcriptional regulation and T-bet and GATA-3 levels remain identical. Thus, Trpm4 is expressed at different levels on T helper cells and plays a distinctive role in T cell function by differentially regulating Ca2+ signaling and NFAT localization. T helper cell gene expression levels when Trpm4 is inhibited by siRNA or dominant negative Trpm4 construct. The ion channel Trpm4 was inhibited in Th1 or Th2 cells using either siRNA or a dominant negative Trpm4 retrovirus and changes in gene profiles were analyzed.
2013-01-23 | E-GEOD-21996 | biostudies-arrayexpress
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2023-10-04 | GSE214871 | GEO
Project description:T-helper cells differentiate from naïve precursors into multiple lineages, including Th1, Th2, Th17 and inducible Treg, in humans and mice. The identification of each lineage is currently determined by examination of a small number of genes encoding hallmark cytokines and/or transcription factors in both species To gain a better understanding of human T-helper cell function we have performed detailed transcriptional profiling of highly polarized Th1 and Th2 cells in both resting and activated states examining gene and miRNA expression Naïve CD4 positive T-cells were isolated from peripheral blood of three different human donors. Cells were differenitated into Th1 and Th2 cells in vitro for 28 days to achieve homogeneous cell lineages. Samples were taken at resting state or activated for 4 hours with PMA/Ionomycin.
2016-08-01 | E-GEOD-43769 | biostudies-arrayexpress
Project description:T-helper cells differentiate from naïve precursors into multiple lineages, including Th1, Th2, Th17 and inducible Treg, in humans and mice. The identification of each lineage is currently determined by examination of a small number of genes encoding hallmark cytokines and/or transcription factors in both species To gain a better understanding of human T-helper cell function we have performed detailed transcriptional profiling of highly polarized Th1 and Th2 cells in both resting and activated states examining gene and miRNA expression
2016-08-01 | GSE43769 | GEO
Project description:Naive CD4+ CD62L+ CD25- T cells were differentiated under TH1 and TH2 conditions for 7 days, restimulated with anti-CD3 and anti-CD28 for 24h and sorted for IFN-gamma (TH1) and IL-4 (TH2) production using cytokine secretion assays.
2009-06-01 | E-MEXP-2153 | biostudies-arrayexpress
Project description:Cathepsin inhibitors have been associated to induce changes in Th1/Th2 polarization; cathepsin B inhibitor CA074 has been reported to induce a Th1 polarization, whereas cathepsin L inhibitor CLIK148 has been reported to induce a Th2 polarization. In this study, we pre-treated bone marrow-derived dendritic cells (BMDC) with CA074Me or CLIK148, followed by stimulation with a known pro-Th1 inducer (CpG) and a known pro-Th2 inducer (TNF-alpha) and analyzed by microarrays the expression of genes acting as pro-Th1 or pro-Th2 mediators.
2018-12-01 | GSE66738 | GEO
Project description:CD4+ T cell differentiation is a key element of the adaptive immune system driving appropriate immune responses by selective differentiation into specialized subsets such as Th1 and Th2 cells. Besides those canonical Th cell lineages, hybrid phenotypes such as Th1/2 cells have been identified in vivo, and their generation could be reproduced in vitro. While master transcription factors like T-bet and GATA-3 regulate and maintain differentiation into the canonical lineages, the transcriptional architecture of hybrid phenotypes is less well understood. In particular, it remains unclear whether a hybrid phenotype implies a mixture of the effects of several canonical lineages for each gene, or rather a bimodal behavior across genes. Th cell differentiation is a dynamic process in which the regulatory factors are modulated over time, but longitudinal studies of Th cell differentiation are sparse. Here, we present a dynamic transcriptome analysis following Th cell differentiation into Th1, Th2 and Th1/2 hybrid cells. We found that only a minority of ~20% of Th cell specific genes clearly shows mixed effects from both Th1 and Th2 cells on Th1/2 hybrid cells. While most genes follow either Th1 or Th2 cell gene expression, another fraction of ~20% of genes follows a Th1 and Th2 cell independent transcriptional program under control of the transcription factors STAT1 and STAT4. Overall, our results emphasize the key role of high-resolution longitudinal data for the characterization of cellular phenotypes.
2022-08-05 | GSE200250 | GEO