Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Blimp-1 moulds the epigenetic architecture of IL-21-mediated autoimmune diseases through an autoregulatory circuit

ABSTRACT: To unravel how Blimp-1 systematically manipulates the global transcriptional landscape in CD4 T cells to contribute to autoimmune progression, we performed RNA sequencing analysis in Blimp-1 transgenic (BTg) or Blimp1-deficient (CKO) NOD mice

ORGANISM(S): Mus musculus

PROVIDER: GSE200545 | GEO | 2022/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Blimp-1 molds the epigenetic architecture of IL-21-mediated autoimmune diseases through an autoregulatory circuit.

Project description:Positive regulatory domain 1 (PRDM1) encodes B lymphocyte-induced maturation protein 1 (BLIMP1), also known as a master regulator of T cell homeostasis. We observed a negative relationship between Blimp-1 and IL-21 based on our previous data that Blimp-1 overexpression in T cells suppresses autoimmune diabetes while Blimp-1-deficient T cells contribute to colitis in NOD mice. Reanalysis of published data sets also revealed an inverse correlation between PRDM1 and IL21 in Crohn's disease. Here, we illustrate that Blimp-1 repressed IL-21 by reducing chromatin accessibility and evicting an IL-21 activator, c-Maf, from the Il21 promoter. Moreover, Blimp-1 overexpression-mediated reduction in permissive chromatin structures at the Il21 promoter could override IL-21-accelerated autoimmune diabetogenesis in small ubiquitin-like modifier-defective c-Maf-transgenic mice. An autoregulatory feedback loop to harness IL-21 expression was unveiled by the evidence that IL-21 addition induced time-dependent Blimp-1 expression and subsequently enriched its binding to the Il21 promoter to suppress IL-21 overproduction. Furthermore, intervention of this feedback loop by IL-21 blockade, with IL-21R.Fc administration or IL-21 receptor deletion, attenuated Blimp-1 deficiency-mediated colitis and reinforced the circuit between Blimp-1 and IL-21 in the regulation of autoimmunity. We highlight the translation of Blimp-1-based epigenetic and transcriptomic profiles applicable to a personalized medicine approach in autoimmune diseases.

| S-EPMC9220827 | biostudies-literature

Blimp-1 moulds the epigenetic architecture of IL-21-mediated autoimmune diseases through an autoregulatory circuit

Project description:Blimp-1 moulds the epigenetic architecture of IL-21-mediated autoimmune diseases through an autoregulatory circuit

| PRJNA825256 | ENA

Analysis of Blimp-1 and Irf-1 genomic binding in wild type and Prdm1/Blimp-1 mutant embryonic gut

2015-07-10 | GSE66069 | GEO

Analysis of Blimp-1 and Irf-1 genomic binding in wild type and Prdm1/Blimp-1 mutant embryonic gut

Project description:The goal of this study was to profile Blimp1 binding in E18.5 small intestine using a Blimp-1-eGFP knock-in allele, and to compare Blimp-1-eGFP genomic binding with Irf-1 genomic binding in normal small intestine. Changes in Irf-1 binding between wild type and Prdm1/Blimp-1 mutant small intestine were also assessed. ChIP-seq was performed for Blimp-1-eGFP in duplicate in E18.5 small intestine expressing the fusion protein using anti-GFP antibody. As a negative control a single anti-GFP ChIP was also performed in wild type small intestine. ChIP-seq for Irf-1 was performed in duplicate in both wild type and Prdm1/Blimp-1 mutant E18.5 small intestine using an anti-Irf-1 antibody. Duplicate IgG ChIP control in wild types was performed as a negative control. All samples had an associated input chromatin sample sequenced.

2015-07-10 | E-GEOD-66069 | biostudies-arrayexpress

IL-10 induces a STAT3-dependent autoregulatory loop in Th2 cells that promotes Blimp-1 restriction of cell expansion via antagonism of STAT5 target genes

Project description:Blimp-1 expression in T cells extinguishes the T follicular helper cell fate and drives terminal differentiation, but also limits autoimmunity. Although various factors have been described to control Blimp-1 expression in T cells, little is known about what regulates Blimp-1 expression in Th2 cells and the molecular basis of its actions. Herein, we report that STAT3 unexpectedly played a critical role in regulating Blimp-1 in Th2 cells. Furthermore, we found that the cytokine IL-10 acted directly on Th2 cells and was necessary and sufficient to induce optimal Blimp-1 expression through STAT3. Together, Blimp-1 and STAT3 amplified IL-10 production in Th2 cells, creating a strong autoregulatory loop that enhanced Blimp-1 expression. Increased Blimp-1 in T cells antagonized STAT5-regulated cell cycle and anti-apoptotic genes to limit cell expansion. These data elucidate the signals required for Blimp-1 expression in Th2 cells and reveal an unexpected mechanism of action of IL-10 in T cells, providing insights into the molecular underpinning by which Blimp-1 constrains T cell expansion to limit autoimmunity.

2018-02-06 | GSE110176 | GEO

miRNA expression in Blimp-1-deficient dendritic cells

Project description:Expression of Blimp-1 was specifically deleted in dendritic cells (DCs) by breeding Blimp-1 flox and CD11c-CRE mice. MiRNA expression was evaluated and compared from DCs, CD4+ T cells and total B cells from spleens of control and Blimp-1 KO mice. Age-matched (6-10 weeks old) female mice from control and Blimp-1 KO mice were sacrificed and spleens were collected. CD11chi/MHCIIhi DCs, CD4+TCRb+ T cells and B220+ B cells were sorted by FACSaria. MiRNA was measured from the total RNA preparation.

2013-09-05 | E-GEOD-40587 | biostudies-arrayexpress

miRNA expression in Blimp-1-deficient dendritic cells

2013-09-05 | GSE40587 | GEO

Epigenetic modifications induced by Blimp-1 regulate CD8+ T cell memory progression during acute virus infection

Project description:Blimp-1 regulates the overall accumulation of virus-specific CD8+ T cells during acute viral infections. Increased proliferation and survival of Blimp-1-deficient CD8+ T cells is promoted by persistent cytokine responsiveness, resulting from sustained expression of CD25 and CD27. Knockdown of these genes reduced the Blimp-1-deficient CD8+ T cell response. Genome-wide ChIP-sequencing analysis identified CD25 and CD27 genes as direct targets of Blimp-1. At the peak of the anti-viral response, but not earlier, Blimp-1 recruited the histone modifying enzymes G9a and HDAC2 to the Il2ra and Cd27 loci, thereby repressing expression of these genes. In the absence of Blimp-1, the Il2ra and Cd27 genes exhibited enhanced histone H3-acetylation and reduced histone H3K9-trimethylation. These data elucidate a central mechanism by which Blimp-1 acts as an epigenetic regulator, enhancing the numbers of short-lived effector cells while suppressing the development of memory precursor CD8+ T cells. NaM-CM-/ve CD8+ T cells from OT-I TCR transgenic Rag1-/- mice were stimulated with anti-CD3 and anti-CD28 for three days in vitro, in the presence of IL-2 to up-regulate Blimp-1 protein. Genome-wide mapping of Blimp-1 binding in mouse CD8+ T cells was conducted.

2013-10-10 | E-GEOD-48358 | biostudies-arrayexpress

Immunological function of Blimp-1 in dendritic cells and relevance to autoimmune diseases.

Project description:Previous studies have identified the immunological functions of transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) in various adaptive immune cell types such as T and B lymphocytes. More recently, it has been shown that Blimp-1 extends its functional roles to dendritic cells (DCs) and macrophages, two cell types belonging to the innate immune system. The protein acts as a direct and indirect regulator of target genes by recruiting chromatin modification factors and by regulating microRNA expression, respectively. In DCs, Blimp-1 has been identified as one of the components involved in antigen presentation. Genome-wide association studies identified polymorphisms associated with multiple autoimmune diseases such as system lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease in PRDM1, the gene encoding Blimp-1 protein. In this review, we will discuss the immune regulatory functions of Blimp-1 in DCs with a main focus on the tolerogenic mechanisms of Blimp-1 required to protect against the development of autoimmune diseases.

| S-EPMC4651792 | biostudies-literature

Epigenetic modifications induced by Blimp-1 regulate CD8+ T cell memory progression during acute virus infection

2013-10-10 | GSE48358 | GEO