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Genome wide H3K4me2 detection after CD74 activation.

ABSTRACT: CD74 (invariant chain), expressed on B cells, is directly involved in shaping the B cell repertoire by regulating their survival in health and disease. Binding of its ligand, macrophage migration inhibitory factor (MIF), induces a cascade that results in CD74 intramembrane proteolysis, and the release of the CD74 intracellular domain (CD74-ICD). CD74-ICD translocates to the nucleus where it induces activation of transcription. In the current study, we characterized the transcription factor activity of CD74-ICD. Following histone modifications we are able to characterize CD74's binding sites as regulatory areas.

ORGANISM(S): Homo sapiens

PROVIDER: GSE181676 | GEO | 2022/11/03

REPOSITORIES: GEO

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Elucidate the role of CD74 in gene transcription regulation by analyzing the genes up or down regulated after 8 hours of activation in human naive B cells.

Project description:CD74 (invariant chain), expressed on B cells, is directly involved in shaping the B cell repertoire by regulating their survival in health and disease. Binding of its ligand, macrophage migration inhibitory factor (MIF), induces a cascade that results in CD74 intramembrane proteolysis, and the release of the CD74 intracellular domain (CD74-ICD). CD74-ICD translocates to the nucleus where it induces activation of transcription. In the current study, we characterize the transcription regulator activities of CD74 by analysing its ability to alter gene expression in mRNA levels.

2022-11-03 | GSE181675 | GEO

The effect of soluble CD74 (sCD74) and recombinant macrophage migration inhibitory factor (MIF) treatment on the gene expression profile in cardiac myofibroblasts

Project description:Co-treatment with soluble CD74 and MIF induced necroptosis in cardiac myofibroblasts. The underlying mechanism of sCD74/MIF-induced necroptosis are still unkown. We used a microarray to identify pathways regulated by co-treatment with sCD74 and MIF .

2018-11-06 | GSE108999 | GEO

The role of CD74 in Hematopoietic Stem Cells

Project description:Hematopoietic stem and progenitors cells (HSPCs) are a small population of undifferentiated cells that have the capacity for self-renewal, and differentiate into all blood cell lineages. These cells are the most useful cells for clinical transplantations and for regenerative medicine. So far, it has not been possible to expand adult hematopoietic stem cells (HSCs) without losing their self-renewal properties. CD74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF), and its mRNA is known to be expressed in HSCs. Here, we demonstrate that mice lacking CD74 exhibit an accumulation of hematopoietic stem cells in the BM due to their increased potential to repopulate and compete for BM niches. Our results suggest that CD74 regulates the maintenance of the HSCs and CD18 expression. Its absence leads to induced survival of these cells, and accumulation of quiescent and proliferating cells. Furthermore, in in-vitro experiments, blocking of CD74 elevated the numbers of HSPCs. Thus, we suggest that blocking CD74 could lead to improved clinical insight into bone marrow transplant protocols, enabling improved engraftment.

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CD74 deficiency impairs Treg accumulation and function in the tumor

Project description:Regulatory T cells (Tregs) are known to actively adapt to the microenvironment in which they reside. However, how Tregs are reshaped in the tumor tissue remains under defined. We observed that in human tumors, Tregs selectively overexpress at the surface CD74, the MHC class II-associated invariant chain. Beyond its role in antigen presentation, CD74 has been described to impact gene transcription and cell migration, however, its role in Treg biology remains unknown. Here, we found that CD74KO Tregs exhibited major defects in the organization of their actin cytoskeleton and intracellular organelles and, consistently, they failed to accumulate in tumors and to suppress the anti-tumoral T-cell response. Strikingly, this phenotype did not result from a generic defect of CD74-deficient Tregs as their phenotype, proliferation, and suppressive function in vitro and in vivo during Graft-versus-Host disease were not affected. Our results reveal a new role for CD74 in Tregs and uncover CD74 potential as novel target to interfere with Treg anti-tumor activity.

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CD74 downregulation in placental macrophages and its influence on trophoblast cells.

Project description:Preeclampsia is a disease of pregnant women, which is characterized by hypertension, proteinuria and chronic inflammation. There is a growing body of evidence that cause of preeclampsia lies within immunological aspect of pregnancy. This study aimed to analyze the role of CD74 in preeclampsia with a focus on its influence on communication between placental macrophages (Hofbauer cells) and trophoblasts. We have found CD74 to be highly dysregulated in preeclamptic placenta by real-time RT-PCR and Western blot methods. We identified Hofbauer cells to express the highest levels of CD74 in placenta by immunofluorescence and flow cytometry and that CD74 in preeclamptic Hofbauer cells is lower than in controls. We have performed a transcriptome analysis on human blood monocyte-derived macrophages that were non- or IL-4-activated and treated with small interfering RNA against CD74 (siRNA CD74) or non-targeting siRNA (siRNA non-targeting) as control.

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Acyloxyacyl hydrolase protects against kidney injury via inhibition of tubular CD74-macrophage crosstalk

Project description:Renal fibrosis is the common pathway in the progression of chronic kidney disease (CKD). Acyloxyacyl hydrolase (AOAH) is expressed in various phagocytes and highly expressed in proximal tubular epithelial cells (PTECs). Research shows that AOAH plays a critical role in infections and chronic inflammatory diseases, although its role in kidney injury is unknown. Here, AOAH expression was examined in human and mouse kidneys, and Aoah-/- mice and single cell RNA sequencing (scRNA-seq) were performed to determine its role in kidney injury induced by folic acid (FA). We found that AOAH expression was positively correlated with estimated glomerular filtration rate (eGFR) while negatively correlated with the degree of renal fibrosis in kidneys of CKD patients. AOAH deletion led to exacerbated kidney injury and fibrosis after FA administration, which was reversed by overexpression of Aoah in kidneys. scRNA-seq revealed that Aoah-/- mice exhibited increased subpopulation of CD74+ PTECs, even though total PTECs were decreased compared to WT mice after FA treatment. Finally, exacerbated kidney injury and fibrosis seen in Aoah-/- mice was attenuated via administration of ISO-1, an inhibitor of macrophage inhibition factor (MIF) and CD74 binding. Thus, our work indicates that AOAH protects against kidney injury and fibrosis by inhibiting renal tubular epithelial cells CD74 signaling pathways. Targeting kidney AOAH represents a promising strategy to prevent renal fibrosis progression.

2023-12-01 | GSE234090 | GEO

CD74 role in transcription regulation

Project description:CD74 role in transcription regulation

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CD74 role in transcription regulation [RNA-seq]

Project description:CD74 activation was previously shown to affect gene transcription. The goal of this study was to reasarch its role as a transcriptor regulator. CD74 was activated in primary CLL cells obtained from patients for 2 and 8 h. mRNA was then extracted, and mRNA-seq was conducted.

2016-12-28 | GSE88956 | GEO

Gene expression profiling in Hepa1c1c7 transfected Cd74 or Tmem54.

Project description:To analyse Cd74 and Tmem54 function as tumor associated genes, we carried out overexpression analysis of Cd74 or Tmem54 using Hepa1c1c7 and investigated downstream genes expression by microarray.

2019-08-20 | GSE123718 | GEO

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2016-12-28 | GSE88955 | GEO

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