CD81 and CD82 expressing tumor_x0002_infiltrating lymphocytes in the NSCLC tumor microenvironment play a crucial role in T-cell activation and cytokine production
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE252148 | GEO | 2024/01/15
REPOSITORIES: GEO
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Project description:CD81 and CD82 expressing tumor_x0002_infiltrating lymphocytes in the NSCLC tumor microenvironment play a crucial role in T-cell activation and cytokine production
| PRJNA1057893 | ENA
Project description:IntroductionTo understand the immune system within the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC), it is crucial to elucidate the characteristics of molecules associated with T cell activation.MethodsWe conducted an in-depth analysis using single-cell RNA sequencing data obtained from tissue samples of 19 NSCLC patients. T cells were classified based on the Tumor Proportion Score (TPS) within the tumor region, and molecular markers associated with activation and exhaustion were analyzed in T cells from high TPS areas.ResultsNotably, tetraspanins CD81 and CD82, belonging to the tetraspanin protein family, were found to be expressed in activated T cells, particularly in cytotoxic T cells. These tetraspanins showed strong correlations with activation and exhaustion markers. In vitro experiments confirmed increased expression of CD81 and CD82 in IL-2-stimulated T cells. T cells were categorized into CD81highCD82high and CD81lowCD82low groups based on their expression levels, with CD81highCD82high T cells exhibiting elevated activation markers such as CD25 and CD69 compared to CD81lowCD82low T cells. This trend was consistent across CD3+, CD8+, and CD4+ T cell subsets. Moreover, CD81highCD82high T cells, when stimulated with anti-CD3, demonstrated enhanced secretion of cytokines such as IFN-γ, TNF-α, and IL-2, along with an increase in the proportion of memory T cells. Bulk RNA sequencing results after sorting CD81highCD82high and CD81lowCD82low T cells consistently supported the roles of CD81 and CD82. Experiments with overexpressed CD81 and CD82 showed increased cytotoxicity against target cells.DiscussionThese findings highlight the multifaceted roles of CD81 and CD82 in T cell activation, cytokine production, memory subset accumulation, and target cell cytolysis. Therefore, these findings suggest the potential of CD81 and CD82 as promising candidates for co-stimulatory molecules in immune therapeutic strategies for cancer treatment within the intricate TME.
| S-EPMC10954780 | biostudies-literature
Project description:We recently found that the tetraspanin family member, CD82, which is aberrantly expressed in chemotherapy-resistant CD34+/CD38− acute myelogenous leukemia (AML) cells, negatively regulates matrix metalloproteinase 9, and plays an important role in enabling CD34+/CD38− AML cells to adhere to the bone marrow microenvironment. This study explored novel functions of CD82 that contribute to AML progression. We employed microarray analysis comparing the gene expression profiles between CD34+/CD38− AML cells transduced with CD82 shRNA and CD34+/CD38− AML cells transduced with control shRNA. Real-time RT-PCR and western blot analysis were performed to examine the effect of CD82 knockdown on the expression of the polycomb group member, enhancer of zeste homolog 2 (EZH2), in leukemia cells. A chromatin immunoprecipitation assay was performed to examine the effect of CD82 expression on the amount of EZH2 bound to the promoter regions of tumor suppressor genes in leukemia cells. We also utilized methylation-specific PCR to examine whether CD82 expression influences the methylation status of the tumor suppressor gene promoter regions in leukemia cells. Microarray analysis revealed that levels of EZH2 decreased after shRNA-mediated depletion of CD82 in CD34+/CD38− AML cells. Moreover, the antibody-mediated blockade of CD82 in leukemia cells lowered EZH2 expression via activation of p38 MAPK signaling, decreased the amount of EZH2 bound to the promoter regions of the tumor suppressor genes, and inhibited histone H3 lysine 27 trimethylation in these promoter regions, resulting in upregulation of the tumor suppressors at both the mRNA and protein levels. The aim of this study was to explore the biological functions of a tetraspanin family protein––CD82–– expressed aberrantly in chemotherapy-resistant CD34+/CD38- acute myelogenous leukemia (AML) cells. Microarray analysis of patient-isolated CD34+/CD38- AML cells revealed that the levels of anti-apoptotic protein BCL2L12 were downregulated after CD82 depletion by specific shRNA. Western blot analysis indicated that BCL2L12 was aberrantly expressed in patient-isolated AML cells and AML cell lines. Furthermore, CD82 blockade by a specific antibody downregulated BCL2L12 in parallel with de-phosphorylation of STAT5 and AKT, while pharmacological inhibition of STAT5 and AKT activation decreased BCL2L12 expression in leukemia cells. In addition, shRNA-mediated downregulation of BCL2L12 increased the levels of cleaved caspase 3and suppressed proliferation of leukemia cells, impairing their engraftment in immunodeficient mice. Taken together, our results indicate that CD82 regulated BCL2L12 expression via STAT5A and AKT signaling and stimulated proliferation and engrafting of leukemia cells, suggesting that CD82 and BCL2L12 may be promising therapeutic targets in AML.
2014-12-30 | GSE64527 | GEO
Project description:The serum hormone levels including T3 and T4 were dramatically decreased in Glis3-null mice due to reduced production of thyroid hormones in thyroid. Gene expression profile and EdU incorporation analysis between WT and Glis3-null mice showed that the cell proliferation was greatly reduced in Glis3-null thyroid. Goitergenic diet (low iodine diet; LID) dramatically enhanced serum TSH levels in both WT and Glis3-null mice, however thyroid goiter was observed in WT mice but not in Glis3-null mice. A subset of genes associated with thyroid hormone production including Pendrin (Slc26a4), Nis (Na+/I– symporter, Slc5a5), Duoxa2 (dualoxidase A2), Tpo (thyroperoxidase), and Dio1 (Deiodinase1) was significantly induced in WT but not in Glis3-null mice by LID feeding.
2017-11-06 | GSE86841 | GEO
Project description:Gene expression analysis of the differentiation process of iPS cells to pancreatic islet cells has revealed that expression of CD82 defines a subset of iPS cell-derived pancreatic endocrine progenitors (EP). While some cell surface proteins such as CD142, CD200 and SUSD2 have been reported as markers of pancreatic progenitor (PP) and EP, CD82+ EP cells are distinct from those PP and EP characterized by the previously identified markers. CD82+ cells isolated from EP cells efficiently differentiated into pancreatic endocrine cells, particularly β cells. Also, CD82+ cells isolated from human cadaver pancreases secreted insulin in response to a high glucose concentration. Furthermore, blocking of CD82 expression by siRNA or inhibition of CD82 in EP by monoclonal antibodies suppressed maturation of β cells, indicating that CD82 plays a role for maturation of EP to β cells. In conclusion, this study identified CD82 not only as a useful marker to isolate β cell precursors but also as an important molecule for functional maturation of β cells.
2022-03-01 | GSE142367 | GEO
Project description:Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues Examination of PR target genes in human umbilical vein endothelial cells (HUVECs) using RNA-seq PR infected only (PR); PR infected followed by ligand treatment (PR+P); PR infected followed by 4h LPS treatment (PR+LPs_4h); PR infected followed by 8h LPS treatment (PR+LPs_8h); PR infected followed by 4h LPS and progesterone treatment (PR+LPS+P_4h); PR infected followed by 8h LPS and progesterone treatment (PR+LPS+P_8h)
2014-01-01 | E-GEOD-46502 | biostudies-arrayexpress
Project description:Subcutaneous white adipose tissue (scWAT) is known to undergo browning in response to cold exposure. The goal of this study is to identify elusive precursors found within scWAT that possess the ability to differentiate into beige adipocytes. A single cell transcriptomics experiment conducted by us identified the tetraspanin CD81 as a marker of adipose precursor cells (APC) that can convert to beige upon cold exposure. However, what distinguishes a CD81 positive APC from its CD81 negative counterpart in the same tissue, or in a different tissue remains unknown. Therefore, we applied bulk RNA-seq to sorted populations of Lineage negative Sca1+, CD81+/ CD81- cells from subcutaneous and visceral WAT, and brown adipose tissue to decipher the molecular underpinnings that render a CD81+ APC residing in scWAT, beige in response to browning.
2020-04-24 | E-MTAB-8435 | biostudies-arrayexpress
Project description:To investigate what stimulates beige progenitor cell proliferation, we performed RNA-seq of primary isolated CD81+ cells (Lin-: Sca1+: CD81+) and CD81- cells (Lin-: Sca1+: CD81-) in the inguinal WAT of mice.
2022-11-04 | GSE201930 | GEO
Project description:The mechanisms underlying the exaggerated distal airway inflammation and hyperresponsiveness that characterize acute exacerbations of asthma are largely unknown. Using BALB/c mouse experimental models, we demonstrated a potentially important role for alveolar macrophages (AM) in the development of an allergen-induced exacerbation of asthma. To induce features of airway inflammation and remodeling characteristic of mild chronic asthma, animals were systemically sensitized and exposed to low mass concentrations (≈3 mg/m(3)) of aerosolized ovalbumin for 30 minutes per day, 3 days per week, for 4 weeks. A subsequent single moderate-level challenge (≈30 mg/m(3)) was used to trigger an acute exacerbation. In chronically challenged animals, cytokine expression by AM was not increased, whereas after an acute exacerbation, AM exhibited significantly enhanced expression of proinflammatory cytokines, including interleukin (IL) 1β, IL-6, CXCL-1, and tumor necrosis factor α. In parallel, there was a marked increase in the expression of several cytokines by CD4(+) T-lymphocytes, notably the Th2 cytokines IL-4 and IL-13. Importantly, AM from an acute exacerbation stimulated the expression of Th2 cytokines when cocultured with CD4(+) cells from chronically challenged animals, and their ability to do so was significantly greater than AM from either chronically challenged or naïve controls. Stimulation was partly dependent on interactions involving CD80/86. We conclude that in an acute exacerbation of asthma, enhanced cytokine expression by AM may play a critical role in triggering increased expression of cytokines by pulmonary CD4(+) T-lymphocytes.
| S-EPMC2947263 | biostudies-literature
Project description:Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues
2014-01-01 | GSE46502 | GEO