Galectin-9 bridges human B cells to vascular endothelium while programming regulatory pathways.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA673913 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12967900.fastq.gz | Fastqsanger.gz | |||
| SRR12967901.fastq.gz | Fastqsanger.gz | |||
| SRR12967894.fastq.gz | Fastqsanger.gz | |||
| SRR12967895.fastq.gz | Fastqsanger.gz | |||
| SRR12967896.fastq.gz | Fastqsanger.gz |
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Project description:Humoral immunity is reliant on efficient recruitment of circulating naive B cells from blood into peripheral lymph nodes (LN) and timely transition of naive B cells to high affinity antibody (Ab)-producing cells. Current understanding of factor(s) coordinating B cell adhesion, activation and differentiation within LN, however, is incomplete. Prior studies on naïve B cells reveal remarkably strong binding to putative immunoregulator, galectin (Gal)-9, that attenuates BCR activation and signaling, implicating Gal-9 as a negative regulator in B cell biology. Here, we investigated Gal-9 localization in human tonsils and LNs and unearthed conspicuously high expression of Gal-9 on high endothelial and post-capillary venules. Adhesion analyses showed that Gal-9 can bridge human circulating and naïve B cells to vascular endothelial cells (EC), while decelerating transendothelial migration. Moreover, Gal-9 interactions with naïve B cells induced global transcription of gene families related to regulation of cell signaling and membrane/cytoskeletal dynamics. Signaling lymphocytic activation molecule F7 (SLAMF7) was among key immunoregulators elevated by Gal-9-binding, while SLAMF7’s cytosolic adapter EAT-2, which is required for cell activation, was eliminated. Gal-9 also activated phosphorylation of pro-survival factor, ERK. Together, these data suggest that Gal-9 promotes B cell – EC interactions while delivering anergic signals to control B cell reactivity.
2020-11-30 | GSE160678 | GEO
Project description:Humoral immunity is reliant on efficient recruitment of circulating naïve B cells from blood into peripheral lymph nodes (LN) and timely transition of naive B cells to high affinity antibody (Ab)-producing cells. Current understanding of factor(s) coordinating B cell adhesion, activation and differentiation within LN, however, is incomplete. Prior studies on naïve B cells reveal remarkably strong binding to putative immunoregulator, galectin (Gal)-9, that attenuates BCR activation and signaling, implicating Gal-9 as a negative regulator in B cell biology. Here, we investigated Gal-9 localization in human tonsils and LNs and unearthed conspicuously high expression of Gal-9 on high endothelial and post-capillary venules. Adhesion analyses showed that Gal-9 can bridge human circulating and naïve B cells to vascular endothelial cells (EC), while decelerating transendothelial migration. Moreover, Gal-9 interactions with naïve B cells induced global transcription of gene families related to regulation of cell signaling and membrane/cytoskeletal dynamics. Signaling lymphocytic activation molecule F7 (SLAMF7) was among key immunoregulators elevated by Gal-9-binding, while SLAMF7's cytosolic adapter EAT-2, which is required for cell activation, was eliminated. Gal-9 also activated phosphorylation of pro-survival factor, ERK. Together, these data suggest that Gal-9 promotes B cell - EC interactions while delivering anergic signals to control B cell reactivity.
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Project description:Microarray analyses were performed in order to determine the effect of galectin-3 ablation on the endothelial transcriptional response in a mouse model of type 2 diabetes. Galectin-3-deficient mice (KO) and wild-type C57BL/6 (WT) were fed a high-fat diet (60% fat calories) or standard chow for 8 weeks. CD105+/CD45- endothelial cells were isolated from the aortae and skeletal muscles of these mice by FACS. Whole genome microarray expression profiling revealed greater transcriptional dysregulation in the endothelium of the KO after high-fat feeding compared to WT. Transcripts dysregulated in the KO endothelium after HFD include those involved in glucose uptake and insulin signaling, oxidative stress, vasoregulation, coagulation, and atherogenesis. Real-time PCR confirmed transcriptional downregulation of the glucose transporter, Glut4, and immunofluorescence staining confirmed reduced GLUT4 protein in the endothelium and mudcle of the KO compared to WT. The transcriptional and histological data was consistent with physiological studies showing exacerbated hyperglycemia and coagulation in the KO. These results suggest that galectin-3 serves a protective role against metabolic dysregulation and endothelial dysfunction in diabetes.
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Project description:Microarray analyses were performed in order to determine the effect of galectin-3 ablation on the endothelial transcriptional response in a mouse model of type 2 diabetes. Galectin-3-deficient mice (KO) and wild-type C57BL/6 (WT) were fed a high-fat diet (60% fat calories) or standard chow for 8 weeks. CD105+/CD45- endothelial cells were isolated from the aortae and skeletal muscles of these mice by FACS. Whole genome microarray expression profiling revealed greater transcriptional dysregulation in the endothelium of the KO after high-fat feeding compared to WT. Transcripts dysregulated in the KO endothelium after HFD include those involved in glucose uptake and insulin signaling, oxidative stress, vasoregulation, coagulation, and atherogenesis. Real-time PCR confirmed transcriptional downregulation of the glucose transporter, Glut4, and immunofluorescence staining confirmed reduced GLUT4 protein in the endothelium and mudcle of the KO compared to WT. The transcriptional and histological data was consistent with physiological studies showing exacerbated hyperglycemia and coagulation in the KO. These results suggest that galectin-3 serves a protective role against metabolic dysregulation and endothelial dysfunction in diabetes. Galectin-3-deficient mice (KO) and wild-type C57BL/6 (WT) were fed either a high-fat diet (60% fat calories) or standard chow diet (12% fat calories) for 8 weeks. Three independent experiments were performed. For each experiment, the aorta and skeletal muscle from 3-4 animals per diet/genotype group were excised and pooled for each tissue. Live, CD105+/CD45- endothelial cells were isolated from the aortic and muscle suspensions by FACS.
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Project description:Endothelin-1 (ET-1), an endothelium-derived vasoconstrictor peptide, plays a role in the pathophysiology of cardiovascular disease. Transgenic mice that overexpress human preproET-1 selectively in the endothelium (eET-1) exhibit endothelial dysfunction, hypertrophic remodeling and vascular inflammation of resistance-size arteries in the absence of blood pressure elevation. To understand the mechanisms whereby ET-1 induces vascular damage, vascular gene expression using DNA microarrays was employed. RNA from mesenteric arteries of female and male young (6-7 weeks) and mature (6-8 months) eET-1 and wild type (WT) mice was isolated and changes in gene expression were determined by genome-wide expression profiling using Illumina microarray. This study revealed a set of genes potentially regulated by ET-1, which might be implicated in ET-1 induced-vascular damage.
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Project description:Endothelin-1 (ET-1), an endothelium-derived vasoconstrictor peptide, plays a role in the pathophysiology of cardiovascular disease. Transgenic mice that overexpress human preproET-1 selectively in the endothelium (eET-1) exhibit endothelial dysfunction, hypertrophic remodeling and vascular inflammation of resistance-size arteries in the absence of blood pressure elevation. To understand the mechanisms whereby ET-1 induces vascular damage, vascular gene expression using DNA microarrays was employed. RNA from mesenteric arteries of female and male young (6-7 weeks) and mature (6-8 months) eET-1 and wild type (WT) mice was isolated and changes in gene expression were determined by genome-wide expression profiling using Illumina microarray. This study revealed a set of genes potentially regulated by ET-1, which might be implicated in ET-1 induced-vascular damage. Samples 1-8: Total RNA obtained from the entire mesenteric arterial tree of young (6-7 weeks) female preproendothelin-1 overexpressing mice compared to age and sex matched wild type littermate controls. Samples 9-16: Total RNA obtained from the entire mesenteric arterial tree of mature (6-8 months) female preproendothelin-1 overexpressing mice compared to age and sex matched wild type littermate controls. Samples 17-24: Total RNA obtained from the entire mesenteric arterial tree of young (6-7 weeks) male preproendothelin-1 overexpressing mice compared to age and sex matched wild type littermate controls. Samples 25-32: Total RNA obtained from the entire mesenteric arterial tree of mature (6-8 months) male preproendothelin-1 overexpressing mice compared to age and sex matched wild type littermate controls.
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Project description:Hyperactive angiogenesis contributes to the immunosuppressive microenvironment important for immunotherapy, and LGALS1-encoed galectin-1 can trigger vascular signaling programs and mediate anti-angiogenic treatment response. However, the mechanism of galectin-1 regulation of angiogenesis is poorly understood. Previous mRNA interactome studies suggested that galectin-1 associated with mRNAs. In this study, we applied the iRIP-seq methodology, an unbiased genome-wide approach to study the RNA binding profiles of galectin-1. The results demonstrate that galectin-1 interacted with a large population of mRNAs with a preferred location towards stop codon, and preferred motifs of UGCA/UGGA and GAGCAG motifs. Galectin-1-bound mRNAs are enriched in cell cycle control and diverse basic biological processes, including its previously reported protein targets H-Ras and also T cell receptors TLR6. Glectin-1 significantly binds to genes in angiogenesis, which included the key pro-angiogenic growth factor VEGFA, angiogenic regulators EGR1 and LAMA5, suggesting that galectin-1 may regulate via its mRNA binding activity. The presented results uncover an previously unrecognized mRNA binding activity of galectin-1; further pursue of this activity could lead to knowledge important for developing therapeutic strategies against cancer and other diseases involved in aberrant angiogenesis.
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