Biology subjects

Marino, K. V.

Publications and source records attributed to Marino, K. V..

3 recordsLinked to original sources

bioRxiv2026

Melanoma suppresses galectin-9-glycan axis in dendritic cells and galectin-9 restoration limits T regulatory cell expansion

Dendritic cells (DCs) are key orchestrators of anti-tumor adaptive immune responses. Their function is tightly regulated by galectins, a family of carbohydrate-biding proteins that decode extracellular glycans into intracellular signaling. Here, we show that exposure to melanoma-conditioned media (CM) induces loss of galectin-9 (gal-9) at the DC surface. Notably, gal-9 loss, independent of transcriptional regulation, was associated with the acquisition of an immunosuppressive phenotype in CD14cDC2 cells following tumor exposure, with higher-molecular weight fractions of the melanoma secretome as mediators. Notably, gal-9 depletion was mirrored with a reduction in gal-9 ligands on the cell surface, particularly GalNAc-containing glycoepitopes, pointing towards a melanoma-exploited gal-9-glycan axis as a DC-evasive strategy. Interestingly, restoring gal-9 surface levels in CM-exposed CD14cDC2 cells prevented the expansion of regulatory T cells (Tregs), postulating gal-9 as a novel immunomodulatory molecule in DC-mediated Treg induction during melanoma progression. Altogether, our data suggest that melanoma-derived factors remodel the DC glycan-gal-9 axis to enhance T cell differentiation towards regulatory phenotypes and dampen anti-tumor immunity. This identifies the gal-9/glycan axis in CD14cDC2 cells as a vulnerable node in melanoma immune evasion and as a potential therapeutic target.

immunology↗

bioRxiv2026

An Altered Glycome Shapes IgA B-Cell Responses and Gut Immunity During Intestinal Inflammation

A healthy gut immune system balances pathogen defense and tolerance to beneficial microbes. This equilibrium is sustained by coordinated mechanisms where B cells (BCs) play a central role, and secretory immunoglobulin A (SIgA) regulates microbiome composition. In ulcerative colitis (UC), impaired tolerogenic pathways result in exaggerated immune activation, epithelial dysfunction, and tissue damage; however, the contribution of BCs to disease pathogenesis remains unclear. Notably, sialylation is crucial to B-cell function, but its relevance in the intestinal IgA B-cell response has been scarcely explored. Here, we show that SIgA from active UC patients displays an inflammation-dependent reduction in (2,6)-sialylation. This desiaylation is recapitulated in dextran sodium sulfate-induced colitis, where IgA plasma cells (IgA+ PCs) and BCs exhibit a similar glycophenotype. Functional analyses reveal that BCs lacking (2,6)-sialylation on N-glycans exhibit defective differentiation into IgA PCs and diminished capacity to suppress intestinal inflammation in vivo, with increased neutrophil infiltration. Moreover, transcriptomic analyses of UC patient samples suggest a synergistic contribution of neuraminidase activity and reduced bioavailability of sialic acid precursors, leading to SIgA desialylation. Collectively, these findings uncover a glycosylation-dependent pathological circuit in which altered sialylation of SIgA and BCs disrupts their function, compromising mucosal homeostasis in intestinal inflammation.

immunology↗

bioRxiv2020

Crystal structures of peanut lectin in the presence of synthetic β-N- and β-S-galactosidesdisclose evidences for the recognition of different glycomimetic ligands

Carbohydrate-lectin interactions are involved in important cellular recognition processes, including viral and bacterial infections, inflammation, and tumor metastasis. Hence, the structural studies of lectin-synthetic glycan complexes are essential for understanding the lectin recognition processes and the further design of promising chemotherapeutics that interfere with sugar-lectin interactions. Plant lectins are excellent models for the study of the molecular recognition process. Among them, peanut lectin (PNA) is highly relevant in the glycobiology field, because of its specificity for {beta}-galactosides, showing high affinity towards the Thomsen-Friedenreich (TF) antigen, a well-known tumor-associated carbohydrate antigen. Given this specificity, PNA is one of the most frequently used molecular probes for the recognition of tumor cell-surface O-glycans. Thus, it has been extensively used in glycobiology for inhibition studies with a variety of {beta}-galactoside and {beta}-lactoside ligands. Herein, crystal structures of PNA are reported in complex with six novel synthetic hydrolytically stable {beta}-N- and {beta}-S-galactosides. These complexes, along with computational simulations, disclosed key molecular binding interactions of the different sugars to PNA at the atomic level, revealing the role of specific water molecules in the protein-ligand recognition. Furthermore, binding affinity studies measured by isothermal titration calorimetry showed dissociation constant values in the micromolar range, as well as a positive glycoside cluster effect in terms of affinity in the case of the divalent compounds. Taken together, this work provides qualitative structural rationale for the upcoming synthesis of optimized glycoclusters, designed for the study of lectin-mediated biological processes. The understanding of the recognition of {beta}-N- and {beta}-S-galactosides with PNA represents a benchmark in protein-carbohydrate interactions since they are novel synthetic ligands not belonging to the family of O-linked glycosides.

biochemistry↗