Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Unveiling signaling pathways inducing MHC class II expression in neutrophils

ABSTRACT: Gram-negative bacillary bacteremia poses a significant threat, ranking among the most severe infectious diseases capable of triggering life-threatening sepsis. Despite the unambiguous involvement of neutrophils in this potentially fatal disease, there are limited data about the molecular signaling mechanisms, phenotype, and function of human neutrophils during the early phase of gram-negative bacillary bacteremia. By using an unbiased proteomics and flow cytometry approach, we identified an antigen-presenting cell (APC)-like phenotype in human peripheral blood neutrophils (PMN) with MHC class II molecule expression in the early phase of bacteremia. Using an in-vitro model of GM-CSF-mediated induction of APC-like phenotype in PMN, we investigated downstream signaling pathways leading to MHC class II expression. GM-CSF stimulation of neutrophils leads to the activation of three major signaling pathways, the JAK-STAT, the mitogen-activated protein kinase (MAPK), and the phosphoinositide 3-kinase (PI3K)-Akt-mTOR pathways, while MHC class II induction is mediated by a MAPK-p38-MSK1-CREB1 signaling cascade and the MHC class II transactivator CIITA in a strictly JAK12 kinase-dependent manner. Our data describing details of signaling pathways inducing MHC class II expression in neutrophils open new possibilities of therapeutic targeting of JAK12 signaling during different stages of gram-negative bacteremia and sepsis.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Alexander Schmidt

PROVIDER: MSV000095939 | MassIVE |

SECONDARY ACCESSION(S): PXD056178

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Dietary suppression of MHC-II expression in intestinal epithelial cells enhances intestinal tumorigenesis

Project description:Little is known about how interactions between diet, intestinal stem cells (ISCs) and immune cells impact the early steps of intestinal tumorigenesis. Here, we show that a high fat diet (HFD) reduces the expression of the major histocompatibility complex II (MHC-II) genes in intestinal epithelial cells including ISCs. This decline in epithelial MHC-II expression in a HFD correlates with reduced diversity of the intestinal microbiome and is recapitulated in antibiotic treated and germ-free mice on a control diet. Mechanistically, pattern recognition receptor (PRR) and IFN g signaling regulate epithelial MHC-II expression where genetic ablation of these signaling pathways dampen MHC-II epithelial expression. Interestingly, upon loss of the tumor suppressor gene Apc in a HFD, MHC-II- ISCs harbor greater in vivo tumor-initiating capacity than their MHC-II+ counterparts when transplanted into immune-component hosts but not immune-deficient hosts, thus implicating a role for epithelial MHC-II-mediated immune surveillance in suppressing tumorigenesis. Finally, ISC-specific genetic ablation of MHC-II in engineered Apc-mediated intestinal tumor models increases tumor burden in a cell autonomous manner. These findings highlight how a HFD perturbs a microbiome – stem cell – immune cell crosstalk in the intestine and contributes to tumor initiation through the dampening of MHC-II expression in pre-malignant ISCs.

2021-08-16 | GSE180949 | GEO

Transcription profiling of human primary B-cell vs monocyte-derived dendritic cells

Project description:Genome-wide RNAi screen reveals new pathways for MHC class II antigen presentation

2010-12-18 | E-MTAB-192 | biostudies-arrayexpress

Oncogene-Expressing senescent melanocytes upregulate MHC Class II, re-localize to the lymph nodes and activate T cells

Project description:OIS is characterized by a stable proliferation arrest and secretion of pro-inflammatory cytokines and chemokines, the senescence-associated secretory phenotype (SASP). Proliferation arrest and the SASP collaborate to enact tumor suppression, the former by blocking cell proliferation and the latter by recruiting immune cells to clear damaged cells. However, the interactions of OIS cells with the immune system are still poorly defined. Here we show that engagement of OIS in primary human melanocytes, specifically by melanoma driver mutations NRASQ61K and BRAFV600E, causes expression of the MHC class II antigen presentation apparatus, via secreted IL1ß signaling and expression of CIITA, a master regulator of MHC class II gene transcription.

2017-06-09 | GSE99397 | GEO

Inhibition of the CtBP complex and FBXO11 enhances MHC class II expression and anti-cancer immune responses [CUT&TAG]

Project description:There is increasing recognition of the prognostic significance of tumor cell major histocompatibility complex (MHC) class II expression in anti-cancer immunity. Relapse of acute myeloid leukemia (AML) following allogeneic stem cell transplantation (alloSCT) has recently been linked to MHC class II silencing in leukemic blasts; however, the regulation of MHC class II expression remains incompletely understood. Utilizing unbiased CRISPR-Cas9 screens, we identify that the C-terminal binding protein (CtBP) complex transcriptionally represses MHC class II pathway genes, while the E3 ubiquitin ligase complex component FBXO11 mediates degradation of CIITA, the principal transcription factor regulating MHC class II expression. Targeting these repressive mechanisms selectively induces MHC class II upregulation across a range of AML cell lines. Functionally, MHC class II+ leukemic blasts stimulate antigen-dependent CD4+ T cell activation and potent anti-tumor immune responses, providing fundamental insights into the graft-versus-leukemia effect. These findings establish the rationale for therapeutic strategies aimed at restoring tumor-specific MHC class II expression to salvage AML relapse post-alloSCT and also potentially to enhance immunotherapy outcomes in non-myeloid malignancies.

2022-10-02 | GSE189771 | GEO

Inhibition of the CtBP complex and FBXO11 enhances MHC class II expression and anti-cancer immune responses [Whole-genome CRISPRscreen]

2022-10-02 | GSE189769 | GEO

Inhibition of the CtBP complex and FBXO11 enhances MHC class II expression and anti-cancer immune responses [Epigenetic CRISPRscreen]

2022-10-02 | GSE189767 | GEO

Inhibition of the CtBP complex and FBXO11 enhances MHC class II expression and anti-cancer immune responses [RNA-Seq]

2022-10-02 | GSE189772 | GEO

Expression data from self-deprived regulatory CD4 T cells

Project description:Disruption of TCR /MHC class II interactions leads rapidly to alterations of the common CD4 Treg transcriptional signature Self-deprived, non-functional Tregs were compare to fully functional Tregs by microarrays. Total T cells from the periphery of WT mice were adoptively transferred into CD3ε-/- recipient mice lacking or not MHC class II molecule expression (MHC II- or MHC II+ recipient mice, respectively). Five days later, peripheral Tregs transferred in MHC II - competent (CD4CD25B6) or - deficient (CD4CD25IIko) recipient were purified for RNA extraction and hybridization on Affymetrix microarrays.

2011-01-20 | E-GEOD-26714 | biostudies-arrayexpress

cDC1 prime and are licensed by CD4+ T cells to induce anti-tumour immunity

Project description:CD4 T cells are thought to help promote anti-tumour responses by ‘licensing’ antigen presenting cells (APCs) that activate CD8 T cells. Conventional type 1 dendritic cells (cDC1s) are responsible for cross-presentation of tumour-derived antigens to CD8 T cells. Prevailing models presume that the cDC1 is licensed by CD4 T cells that are themselves activated by a distinct cDC subset, the cDC2. The recent finding that neoantigens presented by major histocompatibility complex (MHC) class II molecules can promote rejection of tumours that lack MHC class II (MHC-II) surface expression is consistent with an indirect action of CD4 T cells, such as cDC1 licensing. However, no study has directly identified the APC that primes the CD4 T cells responsible for licensing or clearly identified the target of CD4 licensing in vivo. Here, we generated cDC1-specific Cre expressing mouse strain to inactivate or induce expression of MHC-I, MHC-II, or CD40 specifically within the cDC1 lineage. Using a tumour model that relies on CD8 T cells and CD4 T cells for rejection, we discovered that early priming of CD4 T cells against tumour-derived antigens, in contrast to soluble antigens, relied overwhelmingly on the cDC1 and not the cDC2. cDC1 do not simply transport antigen to lymph nodes for processing by cDC2, since lack of MHC-II expression on cDC1 prevented CD4 T cell priming. We also found that CD40 signaling not only affects licensing of cDC1 for CD8 T cell priming, but is also critical for the activation of CD4 T cells. Thus, in the setting of tumour-derived antigens, cDC1 can function as an autonomous platform, capable of priming both CD4 and CD8 T cells and orchestrating their cross-talk required for optimal anti-tumour immunity.

2020-06-11 | GSE152196 | GEO

MHC class II alleles in Great Apes

Project description:MHC class II alleles in Great Apes

| PRJEB27405 | ENA