Innate immune function of galectin-1 as a DAMP
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ABSTRACT:
PROVIDER: PRJNA591290 | ENA |
REPOSITORIES: ENA
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Project description:Galectin-1 is a prototype member of the galectin family of b-galactoside-binding proteins with several immunoregulatory activities (Sundblad et al., 2017). Although this lectin exerts extracellular activities by cross-linking cell surface glycoconjugates, the mechanisms and molecular machinery involved in its secretion are uncertain as it lacks the classical signal sequence required for ER-Golgi release (Camby, 2006; Croci et al., 2014). To assess the global impact of galectin-1 on LPS-induced transcriptomic response, we performed RNAseq analysis of total RNAs from the spleen and the lungs of wild-type and Lgals1-/- mice injected with LPS.
2020-10-29 | GSE140892 | GEO
Project description:Galectin-7 reprograms skin carcinogenesis by fostering innate immune evasive programs
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Project description:Interleukin-1β induces mitochondrial DAMP production to activate STING-dependent innate immune programs
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Project description:Renal fibrosis is a common pathological hallmark of progressive chronic kidney diseases, characterized by persistent inflammation, immune activation, and excessive extracellular matrix deposition. Lectins play a role in modulating immune cell recruitment, amplifying pro-inflammatory signaling, and promoting fibrotic cellular phenotypes. Here, we demonstrate, in a population cohort of individuals with CKD, that the Galectin-3 is robustly expressed in diseased human kidneys and strongly correlates with clinical indices of renal dysfunction. Using the models of adenine induced nephropathy and unilateral ureteral occlusion in mice, we find that Galectin-3 upregulated in kidney collecting tubular cell after injury. Renal fibrosis was significantly reduced in Galectin-3-deficient kidneys, accompanied by lower levels of serum creatinine and blood urea nitrogen and decreased expression of myofibroblast marker α-SMA. RNA sequencing revealed that genes associated with the NF-κB signaling pathway were significantly enriched in the Galectin-3 knockout group. Treatment with GB1107, a selective Galectin-3 inhibitor, also markedly attenuated renal fibrosis, improved renal function and suppressed α-SMA expression. Taken together, our findings suggest that Galectin-3 promotes renal fibrosis through enhancement of inflammatory and fibrotic signaling pathways, and that targeting Galectin-3 may offer therapeutic benefit by preserving kidney function and attenuating interstitial fibrosis.
2026-01-08 | GSE315865 | GEO
Project description:Here we report that exogenous IL-1β induces TBK1-mediated interferon regulatory factor 3 (IRF3) activation and autophagic flux in human myeloid and epithelial cells. IL-1β-induced innate immune activation is dependent upon the DNA sensing pathway adaptor, stimulator of interferon genes (STING), through the recognition of mitochondrial DNA by cyclic GMP-AMP synthase (cGAS). Thus, IL-1β potentiates pathogen-induced interferon production and signal transducer and activator of transcription (STAT) signaling to amplify innate immune responses.
2018-09-21 | GSE120269 | GEO
Project description:Disruption of skin homeostasis by environmental insults activates pathologic circuitries leading to inflammation and carcinogenesis. Galectin-7 (Gal-7), a lectin preferentially expressed in keratinocytes, has been implicated in wound healing and defective skin repair. Here we report using genetically-engineered mouse models and human samples, essential roles for Gal-7 during skin carcinogenesis via coordinated intracellular and extracellular mechanisms. Heightened Gal-7 expression delineated malignant lesions in non-melanoma skin cancer (NMSC) patients and shaped the course of skin carcinogenesis in mice. Intracellularly, increased Gal-7 conferred genomic instability to skin lesions and favored transcription of inflammation-related genes reprogramming the immune landscape toward a myeloid immunoregulatory profile. Extracellularly, Gal-7 accelerated skin carcinogenesis through glycan-dependent induction of monocytic myeloid-derived suppressor cells with enhanced immune regulatory activity. Our findings identify a lectin-driven molecular circuitry that promotes skin carcinogenesis by coupling genomic instability, transcriptional regulation and myeloid immunosuppressive programs, suggesting a potential therapeutic target for the treatment of NMSC.
2023-01-13 | GSE165285 | GEO
Project description:The ability to perform complex bioassays in parallel enables experiments otherwise impossible due to throughput and cost constraints. By way of example, highly parallel chemical-genetic screens using pooled collections of thousands of defined Saccharomyces cerevisiae gene deletion strains are feasible because each strain is barcoded with unique DNA sequences. It is, however, time consuming and expensive to individually barcode individual strains. To provide a simple and general method of barcoding yeast collections, we built a set of donor strains, called Barcoders, with unique barcodes that can be systematically transferred to any S. cerevisiae collection. We applied this technology by generating a collection of barcoded DAmP (Decreased Abundance by mRNA Perturbation) loss-of-function strains comprising 87.1% of all essential yeast genes. This test collection validates both the Barcoders and the DAmP collection as useful tools for genome-wide chemical genetic assays.
2008-07-03 | E-MEXP-1671 | biostudies-arrayexpress
Project description:The goal of this study was to examine differences in gene expression of tumor specific CD8 T cells in an in vivo tumor mouse model after inhibition of galectin-3 protein expression by genetic knockout. Galectin-3 is thought to modulate CD8 T cell response by cross-linking cell surface glycoproteins Galectin-3 is a 31 kD carbohydrate-binding lectin that is over-expressed by many human malignancies. It also modulates T cell responses through a diverse array of mechanisms including induction of apoptosis, TCR cross linking in CD8+ T cells, and T cell receptor (TCR) down regulation in CD4+ T cells. We found that patients responding to a granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting allogeneic pancreatic tumor vaccine developed post immunization antibody responses to galectin-3 on a proteomic screen. We used the HER-2/neu (neu-N) transgenic mouse model to study galectin-3 binding on adoptively transferred high avidity neu-specific CD8+ T cells derived from TCR transgenic mice. Here, we show that galectin-3 binds preferentially to activated antigen-committed CD8+ T cells only in the tumor microenvironment (TME). Galectin-3 deficient mice exhibit improved CD8+ T cell effector function and increased expression of several inflammatory genes when compared with wild type (WT) mice. We also show that galectin-3 binds to LAG-3, and LAG-3 expression is necessary for galectin-3 mediated suppression of CD8+ T cells in vitro. Lastly, galectin-3 deficient mice have significantly elevated levels of circulating plasmacytoid dendritic cells (pDCs), which are superior to conventional dendritic cells (cDCs) in activating CD8+ T cells. Binding of galectin-3 to cell-surface glycoproteins on immune cells suppresses a pro-inflammatory immune response. Thus, inhibiting galectin-3 in conjunction with CD8+ T cell directed immunotherapies should enhance the tumor specific immune response. 3 different experimental groups were studied. Galectin-3 WT CD8 T cells adoptively transferred into Galectin-3 WT mice, galectin-3 WT CD8 T cells transferred into galectin-3 KO mice, and finally galectin-3 KO CD8 T cells transferred into galectin-3 KO mice. Galectin-3 WT CD8 T cells transferred into Galectin-3 WT mice were used as the reference group. Four biological replicates were submitted for each group, and adoptively transfered CD8 T cells were isolated 5 days post-adoptive transfer into tumor-bearing mice treated with a whole cell GM-CSF secreting vaccine. Cells were purified by cell sorting on the Thy1.2 surface marker.
2015-02-19 | E-GEOD-59454 | biostudies-arrayexpress
Project description:Linking Indirect Effects of Cytomegalovirus to Modulation of Monocyte Innate Immune Function
| PRJNA545723 | ENA
Project description:The goal of this study was to examine differences in gene expression of tumor specific CD8 T cells in an in vivo tumor mouse model after inhibition of galectin-3 protein expression by genetic knockout. Galectin-3 is thought to modulate CD8 T cell response by cross-linking cell surface glycoproteins Galectin-3 is a 31 kD carbohydrate-binding lectin that is over-expressed by many human malignancies. It also modulates T cell responses through a diverse array of mechanisms including induction of apoptosis, TCR cross linking in CD8+ T cells, and T cell receptor (TCR) down regulation in CD4+ T cells. We found that patients responding to a granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting allogeneic pancreatic tumor vaccine developed post immunization antibody responses to galectin-3 on a proteomic screen. We used the HER-2/neu (neu-N) transgenic mouse model to study galectin-3 binding on adoptively transferred high avidity neu-specific CD8+ T cells derived from TCR transgenic mice. Here, we show that galectin-3 binds preferentially to activated antigen-committed CD8+ T cells only in the tumor microenvironment (TME). Galectin-3 deficient mice exhibit improved CD8+ T cell effector function and increased expression of several inflammatory genes when compared with wild type (WT) mice. We also show that galectin-3 binds to LAG-3, and LAG-3 expression is necessary for galectin-3 mediated suppression of CD8+ T cells in vitro. Lastly, galectin-3 deficient mice have significantly elevated levels of circulating plasmacytoid dendritic cells (pDCs), which are superior to conventional dendritic cells (cDCs) in activating CD8+ T cells. Binding of galectin-3 to cell-surface glycoproteins on immune cells suppresses a pro-inflammatory immune response. Thus, inhibiting galectin-3 in conjunction with CD8+ T cell directed immunotherapies should enhance the tumor specific immune response.
2015-02-19 | GSE59454 | GEO