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Transcriptomic analysis of resting or activated human CD226- and CD226+ effector memory CD8+ T cell subsets isolated from the peripheral blood of healthy donors.

ABSTRACT: We recently found that loss of the activating receptor CD226 (DNAM-1) was a critical mechanism affecting CD8+ T cell responsiveness to TCR stimulation. To better understand the molecular differences between CD226- and CD226+ CD8+ T cells, we decided to perform a global transcriptional analysis of purified CD226+ and CD226- CD8+ effector memory T cells before and after TCR activation using next generation RNA sequencing. We report here the total RNA sequencing of healthy donor resting CD226- and CD226+ CD8+ Tem cells (n=6/group) or activated (ACT, n=4/group) by α-CD2/CD3/CD28 for 24 hrs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE133397 | GEO | 2020/10/30

REPOSITORIES: GEO

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Transcriptomic analysis of freshly purified human CD226- and CD226+ CD8+ T cell subsets isolated from the peripheral blood of healthy donors.

Project description:We recently found that loss of the activating receptor CD226 (DNAM-1) was a critical mechanism affecting CD8+ T cell responsiveness to TCR stimulation. To better understand the molecular differences between CD226- and CD226+ CD8+ T cells, we decided to perform a global transcriptional analysis of purified naive (Tn, CD62L+CD45RA+), central memory (Tcm, CD62L+CD45RA-) and terminal effector memory (Temra, CD62L-CD45RA+) CD226+ and CD226- CD8+ T cells using next generation RNA sequencing.

2020-10-30 | GSE135291 | GEO

Increased CD226 Expression on CD8+ T cells in Patients with Systemic Sclerosis

Project description:Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular damage, and fibrosis of the skin and internal organs. Because activated and oligoclonally expanded CD8+ T cells can be detected in peripheral blood and lung of SSc patients, effector memory CD8+ T cells may play a critical role for organ involvement in SSc; however, the pathogenic functions of effector memory CD8+ T cells remain incompletely understood. Here we performed DNA microarray analysis of the sort-purified effector memory CD8+ T cells from SSc patients and healthy controls, and showed that the expression of genes related to immune response and cell adhesion, including CD226 (also known as DNAX accessory molecule-1, DNAM-1), was significantly altered. Moreover, detailed analysis of CD226 revealed that CD226highCD8+ T cells were increased in SSc patients (mean, 50.7%) compared with healthy controls (32.9%) and were appreciably associated with the severity of skin sclerosis and interstitial lung disease. Further, CD226highCD8+ T cells from SSc patients produced abundant IL-13 and were positively correlated with the cytotoxic capacity of CD8+ T cells against HUVECs. Finally, the neutralization of CD226 impaired IL-13 production and cytolysis against HUVECs. These findings indicate that upregulated CD226 expression on CD8+ T cells reflects disease severity and are involved in SSc pathogenesis via the production of profibrotic IL-13 and endothelial cell injury, and that CD226 may be a useful target in the treatment of SSc. We first purified effector memory CD8+ T cells (CD3+CD8+CD45RO+CD62L+ cells) from peripheral blood by cell sorting and subsequently performed cDNA microarray analysis of the sort-purified effector memory CD8+ T cells from 9 SSc patients and 5 healthy controls.

2014-12-06 | E-GEOD-63903 | biostudies-arrayexpress

Increased CD226 Expression on CD8+ T cells in Patients with Systemic Sclerosis

2014-12-06 | GSE63903 | GEO

Blocking CD226 regulates ILC2 effector function and alleviates airway hyperreactivity

Project description:Type 2 innate lymphoid cells (ILC2s) play a pivotal role in type 2 asthma. CD226 is a costimulatory molecule involved in various inflammatory diseases. Here, we aimed to investigate CD226 expression and function within human and mouse ILC2s, and to assess the impact of targeting CD226 on ILC2-mediated airway hyperreactivity (AHR). Our findings demonstrated an inducible expression of CD226 in activated ILC2s, enhancing their cytokine secretion and effector functions. Blocking CD226 ameliorates ILC2-dependent AHR in IL-33 and Alternaria Alternata-induced models. Interestingly, CD226 is expressed and inducible in human ILC2s, and its blocking reduces cytokine production. Finally, we showed that peripheral ILC2s in asthmatic patients exhibited elevated CD226 expression compared to healthy controls.Our findings underscore the potential of CD226 as a novel therapeutic target in ILC2s, presenting a promising avenue for ameliorating AHR and allergic asthma.

2024-04-16 | GSE264060 | GEO

Transcriptomic analysis of resting or activated human CD226- and CD226+ effector memory CD8+ T cell subsets isolated from the peripheral blood of healthy donors.

Project description:Transcriptomic analysis of resting or activated human CD226- and CD226+ effector memory CD8+ T cell subsets isolated from the peripheral blood of healthy donors.

| PRJNA551394 | ENA

Transcriptomic analysis of freshly purified human CD226- and CD226+ CD8+ T cell subsets isolated from the peripheral blood of healthy donors.

Project description:Transcriptomic analysis of freshly purified human CD226- and CD226+ CD8+ T cell subsets isolated from the peripheral blood of healthy donors.

| PRJNA558253 | ENA

Global expression profile of spleen DNAM-1+ and DNAM-1- NK cells.

Project description:We determined the global expression profile of DNAM-1+ and DNAM-1- NK cell purified by flow cytometry from 6 different groups of C57BL/6 WT mice. Natural killer (NK) cells comprise a heterogeneous population of cells important for pathogen defense and cancer surveillance. However, the functional significance of this diversity is not fully understood. Here, we demonstrate through transcriptional profiling and functional studies that the activating receptor DNAM-1 (CD226) identifies two distinct NK cell functional subsets: DNAM-1+ and DNAM-1- NK cells. DNAM-1+ NK cells have enhanced Interleukin 15 signaling, proliferate vigorously and produce high levels of inflammatory cytokines. By contrast, DNAM-1- NK cells that differentiate from DNAM-1+ NK cells, have greater expression of NK cell receptor related genes and are higher producers of chemokines. Together our findings highlight the existence of two distinct effector programs in innate lymphocytes controlled through DNAM-1 expression. NK1.1+NKp46+CD3- DNAM-1+ and DNAM-1- NK cell were purified by flow cytometry from 6 different groups of C57BL/6 WT mice and total RNA were extracted

2015-02-26 | E-GEOD-66281 | biostudies-arrayexpress

CD226 and TIGIT cooperate in the differentiation and maturation of human Tfh cells

Project description:The goal was to determine the impact of CD155 signaling through CD226 and TIGIT on Tfh differentiation and function based on gene expression.

2022-02-16 | GSE194293 | GEO

Single-cell RNA-seq of Wild Type and Cd226-/- Thymus Transcriptomes

Project description:Thymi from WT and Cd226 strain knockout mice were digested to obtain single-cell suspensions and then loaded onto microfluidic devices for scRNA-seq. The scRNA-seq libraries were constructed and sequencing outputs were demultiplexed using the bcl2fastq to convert Binary Base Call files into FASTQ format.

2022-01-27 | GSE194270 | GEO

CD8+ CD226high T cells in liver metastases dictate the prognosis of colorectal cancer patients treated with chemotherapy and radical surgery

Project description:In this study, we aimed to assess the prognostic value of CD226 on tumor-infiltrating lymphocytes derived from liver metastases of colorectal cancer (CRC) patients treated with chemotherapy and radical surgery. CD226high expression was associated with a potent immune infiltrate in RNAseq from primary colorectal cancer and liver metastases. CD226 expression contributes to defining the immune contexture of CRC liver metastases and primary tumors. In liver metastases, CD226 expression on CD8 T cells was not specifically co-expressed with other immune checkpoints such as PD1, TIGIT and TIM3. Multivariate Cox regression analysis revealed that CD226 expression on CD8 T cells was an independent prognostic factor (p=0.003) along with CD3 density at invasion margins (p=0.003) and TIGIT expression on CD4 T cells (p=0.019). CD155 was not associated with CD226 prognostic value. Gene expression analysis in a validation dataset confirmed the prognostic value of CD226 selectively in liver metastases but not in primary tumors. Down regulation of CD226 on CD8+ infiltrating lymphocytes in liver microenvironment might be restored by IL-15 treatment. CD226 expression on liver metastases-infiltrating CD8+ contributes selectively to the immune surveillance of liver metastases from CRC and displays a prognostic value for patients undergoing radical surgery.

2022-12-01 | GSE207194 | GEO

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