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Trained immunity is facilitated by T cell-induced CD40-TRAF6 signaling [ChIP-seq]

ABSTRACT: Trained immunity is facilitated by T cell-induced CD40-TRAF6 signaling [ChIP-seq]

PROVIDER: PRJNA948446 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23958630_1.fastq.gz	Fastqsanger.gz
	SRR23958630_2.fastq.gz	Fastqsanger.gz
	SRR23958631_1.fastq.gz	Fastqsanger.gz
	SRR23958631_2.fastq.gz	Fastqsanger.gz
	SRR23958632_1.fastq.gz	Fastqsanger.gz

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Trained immunity is facilitated by T cell-induced CD40-TRAF6 signaling [RNA-seq]

Project description:Trained immunity refers to epigenetic and metabolic changes in innate immune cells following exposure to inflammatory signals, leading to a heightened response to secondary stimuli. Although this innate immune memory contributes to host defense against infections, it can also have maladaptive consequences in a broad range of immune-driven conditions. During the past decade, we have gained an increasingly better understanding of the molecular regulation of trained immunity, but the role of adaptive immune cells in modulation of trained immunity remains largely unknown. Here, we show that T cell interactions contribute to the induction of trained immunity in monocytes and that this mediated by CD40-TRAF6 signaling. Specifically, we found that inhibiting CD40-TRAF6 signaling prevents the induction of functional, transcriptomic, metabolic and epigenetic changes associated with trained immunity. Apart from detailed in vitro studies, we inhibited CD40-TRAF6 signaling in vivo in myeloid cells in a murine heart transplantation model which resulted in prolonged allograft survival. When the animals were additionally treated with costimulatory blockade by CTLA4-Ig, we observed immunological tolerance to the graft. Combined, our study reveals that trained immunity induction is regulated by CD40-TRAF6 signaling between myeloid and adaptive immune cells, and that this signaling can be efficiently leveraged for therapeutic purposes.

2024-08-26 | GSE228183 | GEO

Trained immunity is facilitated by T cell-induced CD40-TRAF6 signaling [ChIP-seq]

2024-08-26 | GSE228182 | GEO

Trained immunity is facilitated by T cell-induced CD40-TRAF6 signaling

Project description:Trained immunity is facilitated by T cell-induced CD40-TRAF6 signaling

| PRJNA948444 | ENA

Trained immunity is facilitated by T cell-induced CD40-TRAF6 signaling [RNA-seq]

Project description:Trained immunity is facilitated by T cell-induced CD40-TRAF6 signaling [RNA-seq]

| PRJNA948447 | ENA

Trained immunity is facilitated by T cell-induced CD40-TRAF6 signaling

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-08-26 | GSE228184 | GEO

Hydroxychloroquine inhibits trained immunity

Project description:Hydroxychloroquine inhibits trained immunity

| PRJNA670179 | ENA

Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling.

Project description:Trained immunity is characterized by histone modifications and metabolic changes in innate immune cells following exposure to inflammatory signals, leading to heightened responsiveness to secondary stimuli. Although our understanding of the molecular regulation of trained immunity has increased, the role of adaptive immune cells herein remains largely unknown. Here, we show that T cells modulate trained immunity via cluster of differentiation 40-tissue necrosis factor receptor-associated factor 6 (CD40-TRAF6) signaling. CD40-TRAF6 inhibition modulates functional, transcriptomic, and metabolic reprogramming and modifies histone 3 lysine 4 trimethylation associated with trained immunity. Besides in vitro studies, we reveal that single-nucleotide polymorphisms in the proximity of CD40 are linked to trained immunity responses in vivo and that combining CD40-TRAF6 inhibition with cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA4-Ig)-mediated co-stimulatory blockade induces long-term graft acceptance in a murine heart transplantation model. Combined, our results reveal that trained immunity is modulated by CD40-TRAF6 signaling between myeloid and adaptive immune cells and that this can be leveraged for therapeutic purposes.

| S-EPMC11536040 | biostudies-literature

scRNAseq of monocytes from Trained immunity experiments

Project description:scRNAseq of monocytes from in vitro Trained immunity experiments stimulated by β-glucan (BG), uric acid (UA), muramyl dipeptide (MDP), oxidized low-density lipoprotein (oxLDL), or RPMI-Control, and respective samples restimulated with Lipopolysaccharide (LPS).

2021-09-30 | E-MTAB-9702 | biostudies-arrayexpress

Hydroxychloroquine inhibits trained immunity

Project description:We demonstrate that hydroxychloroquine inhibits trained immunity at the functional and epigenetic level and is accompanied by reduced expression of interferon-stimulated genes. Trained immunity comprises a functional adaptation induced by epigenetic reprogramming which facilitates the anti-viral innate immune response.

2020-10-21 | GSE159678 | GEO

Trained immunity suppression determines kidney allograft survival

Project description:The innate immune system plays an essential role in regulating the immune responses to kidney transplantation, but the mechanisms through which innate immune cells influence long-term graft survival are unclear. The current study highlights the vital role of trained immunity in kidney allograft survival. Trained immunity describes the epigenetic and metabolic changes that innate immune cells undergo following an initial stimulus, allowing them have a stronger inflammatory response to subsequent stimuli. We stimulated healthy peripheral blood mononuclear cells with pretransplant and posttransplant serum of kidney transplant patients and immunosuppressive drugs in an in vitro trained immunity assay and measured tumor necrosis factor and interleukin 6 cytokine levels in the supernatant as a readout for trained immunity. We show that the serum of kidney transplant recipients collected 1 week after transplantation can suppress trained immunity. Importantly, we found that kidney transplant recipients whose serum most strongly suppressed trained immunity rarely experienced graft loss. This suppressive effect of posttransplant serum is likely mediated by previously unreported effects of immunosuppressive drugs. Our findings provide mechanistic insights into the role of innate immunity in kidney allograft survival, uncovering trained immunity as a potential therapeutic target for improving graft survival.

2024-11-04 | GSE280787 | GEO

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