Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Innate sensor Dhx9 orchestrates TCR signaling and controls CD8 T cell immunity against viral infection [ATAC-Seq]

ABSTRACT: Nuclear sensor molecules of innate cells recognize pathogenic DNA or RNA to activate innate immunity and defense against bacteria and virus infection. Although some sensors exhibit their preliminary functions in T cells, it is still unclear about the underlying mechanism. Here we found a nuclear sensor-Dhx9, was enhanced its expression in effector CD8 T cells. T cell specific deletion of Dhx9 caused an impaired CD8 T cell expansion, memory formation and virus clearance. Mechanically, Dhx9 could directly regulate id2 transcription and in turn control effector CD8 T cell differentiation. Importantly, Dhx9 could bind to Lck protein, mediate Zap70 phosphorylation, and promoting TCR downstream signaling - ERK pathway to protect effector CD8 T cells from apoptosis. The DSRM and DEXDc-Helicase domain is required for Lck binding and Id2 transcription, respectively. Therefore, we revealed a novel regulatory mechanism that innate nuclear sensor regulates T cell fate and function through modulating adaptive pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE161697 | GEO | 2020/11/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Whole genome mRNA analysis of virus-specific CD8+ T cells expressing different levels of Id2-GFP following influenza virus infection

Project description:We speculated that distinct levels of Id2 was deterministic in the transcriptional program of antigen-specific CD8+ T cells. To test this hypothesis, we subjected DbNP366-specific effector CD8+ T cells purified according to their differential expression of Id2-GFP (Id2-GFPint and Id2-GFPhigh) to microarray analysis and compared their gene expression profiles to the differentially expressed genes identified by comparing Id2-deficient and wild-type DbNP366-specific CD8+ T cells. This analysis revealed that the transcriptional program of CD8+ T cell differentiation is exquisitely sensitive to the concentration of Id2. PR8-primed Id2gfp/gfp mice were challenged after one month with influenza intranasally HKx31 virus and analysed on day 9 for the expression of Id2-GFP in DbNP366+CD44+ CD8+ T cells. DbNP366-specific CD8+ T cells were then separated into virus-specific CD8+ T cells that expressed intermediate or high levels of GFP. Purified Id2-GFPintermediate (int) and Id2-GFPhigh DbNP366-specific CD8+ T cells were analysed by mRNA whole genome microarray. Three replicates of each group (Id2-GFPint or Id2-GFPhigh) were analysed.

2013-05-03 | E-GEOD-44140 | biostudies-arrayexpress

Innate sensor Dhx9 directly binds to multiple genes related to effector CD8 T cell differentiation

Project description:Innate sensor Dhx9 directly binds to multiple genes related to effector CD8 T cell differentiation

| PRJNA679186 | ENA

Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT

Project description:T cell antigen receptor (TCR) signaling depends upon the kinases Lck and Zap70. Lck phosphorylates the TCR, facilitating Zap70 recruitment to the stimulated TCR. Lck also phosphorylates Zap70, relieving its auto-inhibition and activating its catalytic domain. Zap70 then phosphorylates the critical adaptors LAT and SLP76 which serve to nucleate key effector molecules required for downstream responses. However, mechanisms facilitating the interaction of Zap70 with its substrates have not been described. We report an evolutionarily conserved proline-rich motif in LAT is important for Zap70-induced phosphorylation of LAT and downstream signaling. This LAT proline-rich motif associated with the Lck SH3 domain, thereby facilitating Zap70-mediated phosphorylation of LAT and downstream functions. Our results suggest Lck orchestrates multiple steps in TCR signaling including the newly described facilitation of the interaction of Zap70 with its substrate LAT. This previously unrecognized feature of TCR proximal signaling may contribute to the development of more immunomodulatory therapies.

2019-11-12 | PXD008258 | Pride

Innate sensor Dhx9 directly binds to multiple genes related to effector CD8 T cell differentiation [ChIP-Seq]

Project description:Innate sensor Dhx9 directly binds to multiple genes related to effector CD8 T cell differentiation [ChIP-Seq]

| PRJNA679181 | ENA

Gene-expression profile of Id2+ versus Id2KO KLRG1lo cells during infection

Project description:CD8+ T cells play a crucial role in the clearance of intracellular pathogens through the generation of cytotoxic effector cells that eliminate infected cells and long-lived memory cells that provide enhanced protection against reinfection. We have previously shown that the inhibitor of E protein transcription factors, Id2, is necessary for accumulation of effector and memory CD8+ T cells during infection. Here we show that CD8+ T cells lacking Id2 did not generate a robust terminally-differentiated KLRG1hi effector population, but displayed a cell-surface phenotype and cytokine profile consistent with memory precursors, raising the question as to whether loss of Id2 impairs the differentiation and/or survival of effector-memory cells. We found that deletion of Bim rescued Id2-deficient CD8+ cell survival during infection. However, the dramatic reduction in KLRG1hi cells caused by loss of Id2 remained in the absence of Bim, such that Id2/Bim double-deficient cells form an exclusively KLRG1loCD127hi memory precursor population. Thus we describe a role for Id2 in both the survival and differentation of normal CD8+ effector and memory populations. Gene-expression analysis of Wild-type, Id2KO, Id2KOBimKO and BimKO effector CD8+ cells on day 6 of Listeria infection. 2 or more replicates per sample were analyzed.

2013-03-07 | E-GEOD-41978 | biostudies-arrayexpress

Gene-expression profile of Id2+ versus Id2KO KLRG1lo cells during infection

2013-03-07 | GSE41978 | GEO

Id2-deficient NK cells acquire a naïve-like fate (ATAC-seq data set)

Project description:All innate lymphoid cells (ILC) constitutively express and require the small helix-loop-helix protein ID2 but the functions of ID2 are not well understood in these cells. Here we show that natural killer (NK) cells, the prototypic ILC, can develop in the absence of ID2 but lose their innate properties and remain as CD27+CD11b- cells that fail to mature into cytotoxic effectors. We show that ID2 broadly limited chromatin accessibility at E protein binding sites near T lymphocyte-associated genes including multiple chemokine receptors, cytokine receptors, and signaling molecules. Moreover, ID2 prevented the conversion of CD27+CD11b- NK cells from a CD8 memory precursor-like chromatin accessibility state toward a naïve-like chromatin accessibility state, and altered their functional capacity. Finally, we demonstrate that increased expression of the naïve T cell-associated helix-loop-helix protein ID3 was required for development of ID2-deficient NK cells, indicating that completely unfettered E protein function is incompatible with NK cell development. These data solidify the roles of ID2 and ID3 as mediators of effector and naïve gene programs, respectively, and revealed a critical role for ID2 in promoting a chromatin state and transcriptional program in CD27+CD11b- NK cells that supports the innate properties of these cells and their ability to undergo cytotoxic effector differentiation.

2018-02-26 | GSE109517 | GEO

Id2-deficient NK cells acquire a naïve-like fate (Affymetrix data set)

2018-02-26 | GSE109456 | GEO

Whole genome mRNA analysis of virus-specific CD8+ T cells expressing different levels of Id2-GFP following influenza virus infection

2013-05-03 | GSE44140 | GEO

Dhx9 controls effector CD8 T cell differetiation program

Project description:Dhx9 controls effector CD8 T cell differetiation program

| PRJNA678442 | ENA