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CD74 deficiency impairs Treg accumulation and function in the tumor

ABSTRACT: CD74 deficiency impairs Treg accumulation and function in the tumor

PROVIDER: PRJNA954341 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24134223_1.fastq.gz	Fastqsanger.gz
	SRR24134223_2.fastq.gz	Fastqsanger.gz
	SRR24134224_1.fastq.gz	Fastqsanger.gz
	SRR24134224_2.fastq.gz	Fastqsanger.gz
	SRR24134225_1.fastq.gz	Fastqsanger.gz

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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.

2024-03-07 | GSE229389 | GEO

IL-34 deficiency impairs FOXP3+ Treg function and increases susceptibility to diseases

Project description:IL-34 deficiency impairs FOXP3+ Treg function and increases susceptibility to diseases

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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 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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Genome wide H3K4me2 detection after CD74 activation.

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Project description:Impact of Tcf1/Lef1 deficiency on Treg cells

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Inherited CD19 deficiency impairs signaling in plasma cells

Project description:Inherited CD19 deficiency impairs signaling in plasma cells

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Transcription profile of WT and LKB1 (encoded by the gene Stk11)-deficient Treg cells

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