Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE212806 | GEO | 2022/10/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Kruppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T cells

Project description:Exhausted CD8 T cells during chronic inflammatory responses against viral infections and cancer are phenotypically and functionally heterogeneous. In particular, CD8 T cells with cytolytic effector function have been recently identified among the exhausted CD8 T cell subsets. However, the regulation of their differentiation and function remains largely unknown. Here, we report that Krüppel-like factor 4 (KLF4) is a critical regulator of the exhaustion process, promoting the cytolytic effector function of exhausted CD8 T cells. KLF4-expressing CD8 T cells in exhaustion contexts showed the features of transitory effector CD8 T cells. Enforced KLF4 expression increased CD8 T cell differentiation into transitory effector subsets and enhanced their antitumor immunity. We further demonstrated that KLF4 also showed a capacity of reinvigorating exhausted CD8 T cells. Last, high KLF4 expression was positively correlated with a favorable prognosis in human patients with cancer. Our study highlights the potential impacts of KLF4 on CD8 T cell exhaustion and antitumor immune therapy. Description KLF4 regulates the exhaustion process by promoting CD8 T cell differentiation into cytolytic transitory effector subsets.

| S-EPMC9699681 | biostudies-literature

Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells [ATAC-Seq]

Project description:Since exhausted CD8 T-cells are known to have a strong epigenetic imprint, which is a major obstacle for reinvigoration, we investigated whether the induced Klf4 expression could change the epigenetic status of the exhausted CD8 T-cells. For this, we performed ATAC-sequencing and compared chromatin landscapes between naïve, in vitro generated effector, exhausted (GFP-induced), and reinvigorated (KLF4-induced) CD8 T-cells.

2022-10-24 | GSE212805 | GEO

Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells [RNA-Seq]

Project description:To identify the role of KLF4 on exhausted CD8 T-cells, we retrovirally transduced Klf4 into OT-I CD8 T-cells on day1 of in vitro exhaustion model and repeatedly treated OVA peptide to induce exhaustion. Then we analyzed the gene expression profiles of these transduced cells by RNA-sequencing.

2022-10-24 | GSE212804 | GEO

Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells [SMART-Seq]

Project description:To identify the role of KLF4 on exhausted CD8 T-cells in vivo, we adoptively transferred PmelI CD8 T-cells transduced with MigRI/Klf4 into MC38-gp100 tumor-bearing Rag2 KO mice on day7. We then isolated tumor-infiltrating PmelI CD8 T-cells on day15 and their gene expression profiles were analyzed by SMART-seq. Also, to investigate the effect of KLF4 deficiency, we isolated PD1+ CD8+ TILs from MC38 tumor-bearing control and Klf4 cKO mice on day14, and SMART-seq was performed.

2022-10-24 | GSE212803 | GEO

Notch regulates cytolytic effector function in CD8+ T cells.

Project description:The maturation of naive CD8(+) T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precise mechanisms regulating CD8(+) effector cell maturation remains poorly understood. In this study, we show that Notch1 regulates the expression of EOMES, perforin, and granzyme B through direct binding to the promoters of these crucial effector molecules. By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B.

| S-EPMC4374745 | biostudies-literature

Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells

Project description:Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells

| PRJNA877351 | ENA

miR-150 Regulates Differentiation and Cytolytic Effector Function in CD8+ T cells.

Project description:MicroRNAs regulate most mammalian genes, and they control numerous aspects of immune system development and function. Their precise roles in the CD8+ T cell response, however, remain unclear. In this report, we show that in the absence of the microRNA miR-150, CD8+ T cells fail to undergo robust expansion and differentiation into short-lived terminal effector cells in response to primary infection with Listeria monocytogenes or Vaccinia virus. Notably, even after transitioning into the memory pool, miR-150(-/-) cells still mount a weaker recall response to secondary infection, and remain less differentiated than their wild-type counterparts. Transcriptome analysis shows miR-150 gene targets are globally upregulated in cells lacking miR-150, and amongst these targets, we found misregulation of genes associated with proliferation and effector cell function. These transcriptome data suggest that miR-150 deficient CD8+ T cells are less efficient in killing infected cells, which we validate experimentally. Together, these results reveal a cell-intrinsic role for miR-150 in the regulation of effector CD8+ T cell fate and function.

| S-EPMC4637875 | biostudies-literature

Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells [SMART-Seq]

Project description:Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells [SMART-Seq]

| PRJNA877360 | ENA

Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells [ATAC-Seq]

Project description:Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells [ATAC-Seq]

| PRJNA877358 | ENA

Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells [RNA-Seq]

Project description:Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells [RNA-Seq]

| PRJNA877359 | ENA