Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spatio-controlled Sialic Acid Polymer Molecular Patterns for Selective Siglecs Modulation and Cytokine Storm Abrogation

ABSTRACT: Cytokine storm is a leading cause of mortality in severe infections and adverse responses to adoptive cell therapiesy. Leveraging multivalent sialic acids (SAs) and the specificity of the SA-Siglec (SA-binding immunoglobulin-type lectins) axis to direct immune cell responses openss a compelling route to efficiently mitigate cytokine storms. However, the optimal configuration of multivalent SAs to maximize Siglec binding affinity and immune-directing activity has yet to be elucidated. Herein, we report Molecular-Patterned Sialic Acid Polymers (MPSPs) Sialic Polymer Molecular Patterns (SPMPMPSPs) , a class of synthetic macromolecular immunomodulators engineered with precise control over polymer backbone conformation, pendant SA densityspacing, and branching topology. This molecular pattern recreates the hierarchical By mimicking the multivalency t architectures of natural glycans while exploiting the modularity of polymer chemistry, and to introduce tunablemolecular controlled SA patterning patterns. Super-resolution fluorescence microscopy and single-molecule spectroscopy confirm structure-specific sialic acid patterns promoteat the molecular scale, SPMPs achieve Siglec-E clustering and high-affinity engagement with Siglec-E, triggering potent inhibitory signaling . The SPMPs robustly and reshape reshaping innate immune cell functions and effectivelyto abrogated cytokine storms. This pattern-encoded macromolecular strategy es establishes a new paradigm for precise immune modulation and offering a framework for materials-based interventions in inflammatory disorders.

ORGANISM(S): Mus

PROVIDER: GSE312405 | GEO | 2025/12/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Targeting stromal cell sialylation reverses T cell mediated immunosuppression in the tumor microenvironment

Project description:Immunosuppressive tumor microenvironments (TME) reduce the effectiveness of immune responses in cancer. Mesenchymal stromal cells (MSC), precursors to cancer-associated fibroblasts (CAFs), dictate tumor progression by enhancing immune cell suppression in colorectal cancer (CRC). Hyper-sialylation of glycans promotes immune evasion in cancer through binding of sialic acids to their receptors, Siglecs, expressed on immune cells that results in inhibition of effector functions. The role of sialylation in dictating MSC/CAF immunosuppression in the TME is unknown. In this study, we show that tumor-conditioned stromal cells have increased sialyltransferase expression, α2,3/6-linked sialic acid and Siglec ligands. Tumor-conditioned stromal cells and CAFs induce exhausted immunomodulatory PD-1, Siglec-7 and Siglec-9-expressing T cell phenotypes. In vivo, targeting stromal cell sialylation reverses stromal cell-mediated immunosuppression, as evidenced by infiltration of CD25 and granzyme B-expressing T cells in the tumor and draining lymph node. Targeting stromal cell sialylation may overcome immunosuppression in the CRC TME.

2023-05-22 | GSE229054 | GEO

Targeting cancer glycosylation repolarizes tumor-associated macrophages allowing effective immune checkpoint blockade

Project description:Immune checkpoint blockade (ICB) has significantly improved the prognosis of cancer patients, but the majority experience limited benefit, evidencing the need for new therapeutic approaches. Upregulation of sialic acid-containing glycans, termed hypersialylation, is a common feature of cancer-associated glycosylation, driving disease progression and immune escape via the engagement of Siglec-receptors on tumor-infiltrating immune cells. Here, we show that tumor sialylation correlates with distinct immune states and reduced survival in human cancers. The targeted removal of Siglec-ligands in the tumor microenvironment, using an antibody-sialidase conjugate, enhances anti-tumor immunity and halts tumor progression in several mouse tumor models. Using single-cell RNA sequencing, we reveal desialylation mechanistically to repolarize tumor-associated macrophages (TAMs) and identify Siglec-E on TAMs as the main receptor for hypersialylation. Finally, we show genetic and therapeutic desialylation, as well as loss of Siglec-E, to synergize with ICB. Thus, therapeutic desialylation represents a novel immunotherapeutic approach, shaping macrophage phenotypes and augmenting the adaptive anti-tumor immune response.

2022-11-24 | GSE208133 | GEO

Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b

Project description:Sialic acid-binding Ig-like lectin 15 (Siglec-15) is emerging as an immune modulator and target for cancer immunotherapy. However, limited knowledge regarding its mechanism of action and structure, or its binding partners with T cells, restrains the development of drug candidates that could unleash its full therapeutic potential. Here, we determine the crystal structure of Siglec-15 and delineate its binding epitope by co-crystallization with an anti-Siglec-15 blocking antibody. Saturation transfer-difference nuclear magnetic resonance (STD-NMR) spectroscopy assisted with molecular dynamics simulations reveals the binding mode of Siglec-15 to (2,3)- and 2,6)- linked sialic acids and to the cancer-associated sialyl-Tn (STn) glycoform. Binding of Siglec-15 to T cells, which lack STn expression, depends on the presence of (2,3)- and 2,6)- linked sialoglycans. We identify the leukocyte integrin CD11b as a binding partner of Siglec-15 on human T cells. Collectively, these data provide an integrative understanding of the structural features of Siglec-15 and underscore glycosylation as an additional layer of control of T cell responses.

2023-07-20 | PXD042009 | Pride

Next-generation sequencing of human monocyte-derived dendritic cells stimulated with sialic acid glycodendrimers in the absence or presence of LPS

Project description:To investigate whether a2-3 sialic acid dendrimers that bind to Siglec-9 would alter signalling and reprogramming of human monocyte-derived dendritic cells with and without LPS.

2021-06-23 | GSE168887 | GEO

Siglec-G suppresses CD8+ T cells responses through metabolic rewiring and can be targeted to enhance tumor immunotherapy

Project description:CD8+ T cells play a critical role in cancer immune-surveillance and pathogens elimination. However, their effector function can be severely impaired due to inhibitory receptors such as PD-1 and Tim-3. Here we identify Siglec-G as a novel coinhibitory receptor that limits CD8+ T cell function. Siglec-G is highly expressed on tumor-inﬁltrating T cells and is enriched in the exhausted T cell subset. Ablation of Siglec-G enhances the efficacy of adoptively transferred T cells and CAR T cells to repress the growth of solid tumors. Mechanistically, sialic acids on tumor cells trigger Siglec-G-SHP2 axis in CD8+ T cells, and impairs metabolic reprogramming from OXPHOS to glycolysis, which dampens CTL activation, expansion and cytotoxicity. These findings deﬁne a critical role for Siglec-G in inhibiting CD8+ T cell responses, which strongly suggests its therapeutic effect in adoptive T cell therapy and tumor immunotherapy.

2024-12-18 | GSE272544 | GEO

Immune cells surveil aberrantly sialylated O-glycans on megakaryocytes to regulate platelet count

Project description:Immune thrombocytopenia (ITP) is a common platelet disorder in pediatric patients. Pediatric and adult ITP have been associated with sialic acid alterations, but the pathophysiology of ITP remains elusive, and ITP is often a diagnosis of exclusion. Our analysis of pediatric ITP plasma samples showed increased anti-Thomsen-Friedenreich antigen (TF-antigen) antibody representation, suggesting increased exposure of the typically sialylated and cryptic TF-antigen in these patients. The O-glycan sialyltransferase St3gal1 add sialic acid specifically on the TF-antigen. To understand if TF-antigen exposure associates with thrombocytopenia, we generated a mouse model with targeted deletion of St3gal1 in megakaryocytes (MK) (St3gal1MK-/-). TF-antigen exposure was restricted to MKs and resulted in thrombocytopenia. Deletion of Jak3 in St3gal1MK-/- mice normalized platelet counts implicating involvement of immune cells. Interferon-producing Siglec H-positive bone marrow (BM) immune cells engaged with O-glycan sialic acid moieties to regulate type I interferon (IFN-I) secretion and platelet release (thrombopoiesis), as evidenced by partially normalized platelet count following and inhibition of interferon and Siglec H receptors. Single cell RNAseq determined that TF-antigen exposure by MKs primed St3gal1MK-/- BM immune cells to release IFN-I. Single cell RNAseq further revealed a new population of immune cells with a plasmacytoid dendritic cell (pDC)-like signature and concomitant upregulation of immunoglobulin re-arrangement gene transcripts Igkc and Ighm, suggesting additional immune regulatory mechanisms. Thus, aberrant TF-antigen moieties, often found in pathological conditions, regulate immune cells and thrombopoiesis in the BM, leading to reduced platelet count.

2021-06-29 | GSE179067 | GEO

Spatio-controlled Sialic Acid Polymer Molecular Patterns for Selective Siglecs Modulation and Cytokine Storm Abrogation

Project description:Spatio-controlled Sialic Acid Polymer Molecular Patterns for Selective Siglecs Modulation and Cytokine Storm Abrogation

| PRJNA1373259 | ENA

Proximity Labeling and Genetic Screening Reveals the Role of DSG2/Siglec-9 Axis in Suppressing Macrophage Phagocytosis

Project description:In current study, we have established a combined strategy using proximity labeling and genetic screening to identify the cellular ligands of Siglec-9. Our use of proximity labeling using APEX2 fusion proteins followed by quantitative proteomics allowed us to efficiently label and enrich cell surface protein ligands that directly interact with Siglec-9 via sialic acid moieties. By combining with CRISPR knockout screening, we were able to identify functionally significant ligands. We confirmed at the cellular level that DSG2 expressed on cell surfaces directly interacts with Siglec-9, and this interaction is mediated by site-specific N-glycans on the ECD of DGS2. We also demonstrated the binding between DSG2 on A375 melanoma cells and Siglec-9 on macrophages contributes significantly to Siglec-9 signaling and blocking the DSG2-Siglec-9 axis by either DSG2 knockdown or anti-Siglec-9 antibody, releases immune-suppression and increases phagocytosis. Our findings revealed an important ligand in cancer cells for the immunosuppressive receptor Siglec-9, and suggest the potential of disrupting DSG2-Siglec-9 signaling axis in anti-cancer therapy.

2024-12-23 | PXD051557 | Pride

Ablation of CD22 Induces a Pro-Inflammatory Transcriptome Shift and Endocytic Deficits in M2-like Macrophages

Project description:The interactions between environmental glycans and glycan-binding proteins modulate a host of processes across biological systems. The Siglec/sialic acid axis has gained increasing attention as an immunologic checkpoint due to its involvement with reducing inflammatory processes and promoting tumor growth. Siglec-2, or CD22, has been extensively characterized as a co-receptor for the B cell receptor (BCR) and is critical for the prevention of self-reactive B cell responses through its recognition of α2,6-linked sialic acids. More recently, CD22 has emerged as an important receptor for macrophage biology. Here, we investigate the consequences of genetic ablation of CD22 in macrophages (CD22KO). Aged CD22KO mice developed a fatty liver phenotype similar to that seen in aged animals lacking hepatocyte α2,6-sialylation (HcKO). CD22KO bone marrow-derived macrophages (BMDMs) exhibited few differences in canonical markers of M1-like and M2-like polarization, but M2-like CD22KO BMDMs showed a pro-inflammatory shift in transcriptome and a reduction in endocytic and efferocytotic capacity. These data suggest that CD22 in M2-like macrophages is strongly associated with a homeostatic transcriptional profile, and directly participates in immunologically silent housekeeping functions such as clearance of sialylated-self debris through the Siglec-sialic acid axis.

2025-12-04 | GSE310152 | GEO

HIV-Induced Sialoglycans on Infected Cells Promote Immune Evasion from Myeloid Cell-Mediated Killing

Project description:Sialic acid-containing glycans (sialoglycans) on pathological cells interact with Siglecs, glyco-immune checkpoint receptors expressed on myeloid cells such as monocytes and neutrophils. This interaction suppresses the cytotoxic functions of these immune cells. We show that HIV infection reprograms the glycosylation machinery of infected cells to increase the expression of specific sialoglycan ligands for Siglecs-3, -7, and -9. These ligands engage Siglecs on myeloid cells, impairing their ability to target HIV-infected cells. Selective disruption of these interactions using 10-1074-Sia, an HIV-specific antibody conjugated to sialidase—an enzyme that removes sialic acids—significantly enhances monocyte- and neutrophil-mediated killing of HIV-infected cells in autologous assays. Treatment with 10-1074-Sia in humanized mice infected with HIV reduces viral load and decreases inflammation. These findings reveal a novel immune evasion mechanism exploited by HIV to evade myeloid cell immune surveillance and highlight the potential of targeting sialoglycan-Siglec interactions to improve immune clearance of HIV-infected cells.

2025-11-20 | GSE290132 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data