Unknown,Transcriptomics,Genomics,Proteomics

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Effects Of Simulated Space Conditions On CD4+ T Cells: A Multi Modal Analysis

ABSTRACT: The goal of this study was to isolate CD4+ T cells from the blood of healthy volunteers and expose them to simulated space stressors in a single and combined manner to investigate their effects on T cell activation, gene expression, and cytokine production. Cytokine levels for Th1, Th2, and Treg cell populations were measured using multiplex Luminex assays to assess functional changes in T cell subsets under simulated space conditions. Furthermore, this study aimed to analyze gene expression patterns using RNA-seq to identify key genes and pathways involved in T cell activation and the immune response that are significantly altered in response to simulated space conditions. Proteomic analysis was also conducted to examine changes in protein expression and modifications that may occur in CD4+ T cells under simulated space conditions. Overall, this study aimed to provide a comprehensive understanding of the effects of simulated space conditions on CD4+ T cells and their role in the immune response.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Bjorn Baselet

PROVIDER: E-MTAB-14151 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Different naïve or memory cell subpopulations (i.e., central memory/CM, effector memory/EM, or terminally differentiated effector memory/EMRA) are involved in asthma development, and they display variable levels of the CD26 (dipeptidyl peptidase 4/DPP4). The phenotype and/or severity of the disease could drive to a phenotypic shift in naïve/memory lymphocyte subsets. Therefore, the aim of our work was to evaluate the association of the phenotype and severity of asthma with the relative frequency of CD26-/lo, CD26int, and CD26hi subsets within CD4+ effector T cells (Teff), total CD4- lymphocytes, γδ-T cells, NK cells, and NKT cells. For that, flow cytometry analyses were performed in peripheral blood samples from healthy donors (N=30) and asthma patients (N=119) with different phenotypes/severities. To avoid a priori bias, we have performed a K-means clustering analysis including clinical and flow cytometry data, resulting in four groups, two of them with opposite inflammatory profiles (eosinophilic vs. neutrophilic). CD4-CD26hi cells were reduced in neutrophilic asthma, and negatively correlated with degree of systemic inflammation. Interestingly, the eosinophilic group displayed a general expansion of CD26-/lo lymphocyte subsets. The expansion of CD4+CD26-/lo Teff cells with a TEM/TEMRA phenotype was confirmed in asthma, especially in atopic patients. Further characterisation of this subset by LC MS/MS revealed upregulated levels of innate (e.g., MPO and RNASE2) and cytoskeleton/extracellular matrix (e.g., MMP9, ACTN1) proteins, which matches its terminally differentiated phenotype. Validation by immunofluorescence confirmed the presence of many of these proteins in CD4+ T cells, as well as an enrichment in “flower-like” nuclei and MMP9/RNASE2 levels in CD4+CD26-/lo Teff compared to CD4+ T lymphocytes. Therefore, there is an association between CD26 levels in different lymphocyte subsets and asthma phenotypes/severities. CD4+CD26-/loTEMRA cells expressing innate proteins specific to eosinophils/neutrophils could be relevant in sustaining long-term inflammation in adult allergic asthma.

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Effects Of Simulated Space Conditions On CD4+ T Cells: A Multi Modal Analysis

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