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FXR protects against neonatal sepsis via enhancing the immunosuppressive function of MDSCs

ABSTRACT: FXR protects against neonatal sepsis via enhancing the immunosuppressive function of MDSCs

PROVIDER: PRJNA1223799 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32342219_1.fastq.gz	Fastqsanger.gz
	SRR32342219_2.fastq.gz	Fastqsanger.gz
	SRR32342220_1.fastq.gz	Fastqsanger.gz
	SRR32342220_2.fastq.gz	Fastqsanger.gz
	SRR32342221_1.fastq.gz	Fastqsanger.gz

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FXR protects against neonatal sepsis via enhancing the immunosuppressive function of MDSCs

Project description:The presence of myeloid-derived suppressor cells (MDSCs) during the early postnatal period plays a protective role against neonatal inflammation. However, the mechanisms regulating neonatal MDSCs remain to be fully elucidated. In this study, we report that the bile acid receptor Farnesoid X receptor (FXR) acts as a pivotal positive regulator of neonatal MDSCs. Using FXR-deficient (FXR-/-) mice and FDA-approved FXR agonist obeticholic acid (OCA), we demonstrated that FXR deficiency impairs the immunosuppressive and antibacterial functions of neonatal MDSCs, thereby exacerbating the severity of neonatal sepsis. Adoptive transfer of MDSCs alleviates sepsis severity in FXR-/- neonatal pups. Mechanistic studies reveal that HIF1a, a well-established regulator of MDSCs, is a direct transcriptional target of FXR. Patients with neonatal sepsis displayed reduced MDSC frequencies and impaired expression of FXR and HIF-1α, which was negatively correlate with the clinical parameters. These observations highlight the important role of FXR in neonatal MDSCs and its therapeutic potential in neonatal sepsis.

2025-05-20 | GSE289598 | GEO

Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of MDSCs in Newborns

Project description:Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of MDSCs in Newborns

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Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of MDSCs in Newborns [cell]

Project description:Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of MDSCs in Newborns [cell]

| PRJNA827582 | ENA

Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of MDSCs in Newborns [tissue]

Project description:Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of MDSCs in Newborns [tissue]

| PRJNA827584 | ENA

Cholesterol 25-hydroxylase enhances immunosuppressive function of MDSCs in colorectal cancer

Project description:Myeloid-derived suppressor cells (MDSCs) represent a substantial population of immunosuppressive cells within the tumor microenvironment (TME) of colorectal cancer. Previous studies have established a strong association between the immunosuppressive activity of MDSCs and the reprogramming of cholesterol metabolism; however, the underlying mechanisms remain to be fully elucidated. In this study, we identified that cholesterol 25-hydroxylase (CH25H) and its metabolite, 25-hydroxycholesterol (25HC), are significantly elevated in MDSCs associated with colorectal cancer. The knockdown of CH25H led to a decrease in the immunosuppressive capabilities of MDSCs, which was linked to the inhibition of Arginase-1 (ARG1) expression; conversely, the administration of 25HC counteracted this effect. Mechanistically, 25HC was shown to downregulate the Cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) (cGAS-STING) pathway and its downstream signaling component, TANK binding kinase 1(TBK1). Upon phosphorylation and activation, TBK1 inhibited ARG1 production. In summary, our findings indicate that CH25H-mediated accumulation of 25HC enhances the immunosuppressive function of MDSCs and promotes immune evasion in colorectal cancer by suppressing the STING-TBK1- receptor-interacting protein kinase 3(RIPK3) signaling axis. This study uncovers a novel signaling pathway involving CH25H and STING in tumor immunomodulation and suggests that targeting cholesterol metabolism may provide a promising therapeutic strategy for colorectal cancer immunotherapy.

2025-11-14 | GSE284266 | GEO

Expression data from MDSCs at different time points during tumor progression

Project description:Myeloid-derived suppressor cells (MDSCs) are increased by tumor-derived factors and suppress anti-tumor immunity. MDSCs obtained at a late time point after tumor injection had stronger suppressive activity than MDSCs obtained at an early time point, as measured by T cell proliferation assays. To find factors in MDSCs that change during tumor growth, we analyzed gene expression profiles from MDSCs at different time points after tumor injection. We found that immune response-related genes were down-regulated, but pro-tumor function-related genes were up-regulated in both Mo-MDSCs and PMN-MDSCs at the late time point. Among differentially expressed genes, FK506 binding protein 51 (FKBP51), which is a member of the immunophilin protein family and plays a role in immunoregulation, was increased in the Mo- and PMN-MDSCs isolated from the late time points. Experiments using siRNA and a chemical inhibitor of FKBP51 revealed that FKBP51 contributes to the regulation of the suppressive function of MDSCs by increasing iNOS, ARG1, and ROS levels and enhancing NF-kappaB activity. Collectively, our data suggest that FKBP51 is a novel molecule that can be targeted to regulate the immunosuppressive function of MDSCs. To identify the factors that licensed MDSCs to be more suppressive as tumors grow, we analyzed gene expression profiles in the two subsets of MDSCs at different time points (3wks, 6wks) during tumor progression. CD11b+Ly-6C(high)Ly-6G(low) Mo-MDSCs and CD11b+Ly-6C(low)Ly-6G(high) PMN-MDSCs were sorted from pooled spleens of naÃ¯ve mice and Her-2/CT26 tumor-bearing mice. Total RNA was purified and gene expression was analyzed by the Affymetrix GeneChipÂ® Mouse Gene 1.0 ST Array.

2012-03-29 | E-GEOD-35398 | biostudies-arrayexpress

Comparative analysis of monocytes from healthy donors, patients with metastatic breast cancer, sepsis or tuberculosis.

Project description:Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, which increase in cancer patients. The molecular mechanism behind their generation and function is unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer, the presence and relevance of monocytic-MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of functional blood Mo-MDSCs in breast cancer patients before they acquire a typical Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell surface phenotype (CD14+HLA-DRlow/-Co-receptorlow/-) increased significantly first during disease progression and correlated to metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising the Mo-MDSC population, from patients with metastatic breast cancer resemble the reprogrammed immunosuppressive monocytes in patients with severe infections, both by their surface and functional phenotype but also at their molecular gene expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast cancer patients may represent a novel and simple biomarker for assessing disease progression. Peripheral blood monocytes were isolated using magnetic cell sorting from 4 patients with metastatic breast cancer, 3 healthy controls, 3 patients with sepsis and 3 patients with active tuberculosis were immediately frozen at -80C in TRIZOL.

2015-02-03 | E-GEOD-65517 | biostudies-arrayexpress

Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of MDSCs in Newborns [tissue]

Project description:Adenosine-induced MDSCs represent an essential immune axis for intestinal homeostasis in newborns.

2022-04-18 | GSE200929 | GEO

Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of MDSCs in Newborns [cell]

Project description:Adenosine-induced MDSCs represent an essential immune axis for intestinal homeostasis in newborns.

2022-04-18 | GSE200930 | GEO

Bulk RNA-Seq for MDSCs

Project description:Myeloid-derived suppressor cells (MDSCs) as a population of myeloid cells enriched in cancer patients with immunosuppressive function. Further studies have determined that MDSCs are comprised of two groups: polymorphonuclear-MDSCs (G-MDSCs) and monocytic-MDSCs (M-MDSCs). We used a microbeads kit (Miltenyi) to isolate G-MDSCs and M-MDSCs with markers Ly6c2-Ly6g+CD11b+ and Ly6c2+Ly6g-CD11b+, respectively. And then using bulk RNA-seq to anlysis the enrichment gene expression in G-or M-MDSC which from wild type, APCmin mutant adenoma and immune deffiency mice.

2022-08-21 | GSE136258 | GEO

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