Galectin-9 interacts with Vamp-3 to regulate cytokine secretion in dendritic cells

Santalla Méndez, Rui; Rodgers Furones, Andrea; Classens, René; Fedorova, Kristina; Haverdil, Manon; Canela Capdevila, Marta; van Duffelen, Anne; Spruijt, Cornelia G.; Vermeulen, Michiel; ter Beest, Martin; van Spriel, Annemiek B.; Querol Cano, Laia

doi:10.1007/s00018-023-04954-x

Cited by 5 publications

(1 citation statement)

References 63 publications

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“…Among the varied existing innate immune cell populations, there are monocytes, macrophages, granulocytes, and polymorphonuclear (PMN) cells consisting of neutrophils, eosinophils, mast cells, and basophils; there are also dendritic cells and innate lymphoid cells (ILCs) [7][8][9][10][11][12]. ILCs have the particularity of being lymphocytes that have activating and inhibiting receptors and are susceptible to cytokine stimulation.…”

Section: Introduction To Unconventional T Cell Subtypes Inkts and Cd1...mentioning

confidence: 99%

Natural Killer T Cell Diversity and Immunotherapy

Tognarelli,

Gutiérrez-Vera,

Palacios

et al. 2023

Cancers

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Invariant natural killer T cells (iNKTs), a type of unconventional T cells, share features with NK cells and have an invariant T cell receptor (TCR), which recognizes lipid antigens loaded on CD1d molecules, a major histocompatibility complex class I (MHC-I)-like protein. This interaction produces the secretion of a wide array of cytokines by these cells, including interferon gamma (IFN-γ) and interleukin 4 (IL-4), allowing iNKTs to link innate with adaptive responses. Interestingly, molecules that bind CD1d have been identified that enable the modulation of these cells, highlighting their potential pro-inflammatory and immunosuppressive capacities, as required in different clinical settings. In this review, we summarize key features of iNKTs and current understandings of modulatory α-galactosylceramide (α-GalCer) variants, a model iNKT cell activator that can shift the outcome of adaptive immune responses. Furthermore, we discuss advances in the development of strategies that modulate these cells to target pathologies that are considerable healthcare burdens. Finally, we recapitulate findings supporting a role for iNKTs in infectious diseases and tumor immunotherapy.

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Section: Introduction To Unconventional T Cell Subtypes Inkts and Cd1...mentioning

confidence: 99%

Natural Killer T Cell Diversity and Immunotherapy

Tognarelli,

Gutiérrez-Vera,

Palacios

et al. 2023

Cancers

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Intracellular galectin interactions in health and disease

Jacob,

Gorek

2024

Semin Immunopathol

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In the galectin family, a group of lectins is united by their evolutionarily conserved carbohydrate recognition domains. These polypeptides play a role in various cellular processes and are implicated in disease mechanisms such as cancer, fibrosis, infection, and inflammation. Following synthesis in the cytosol, manifold interactions of galectins have been described both extracellularly and intracellularly. Extracellular galectins frequently engage with glycoproteins or glycolipids in a carbohydrate-dependent manner. Intracellularly, galectins bind to non-glycosylated proteins situated in distinct cellular compartments, each with multiple cellular functions. This diversity complicates attempts to form a comprehensive understanding of the role of galectin molecules within the cell. This review enumerates intracellular galectin interaction partners and outlines their involvement in cellular processes. The intricate connections between galectin functions and pathomechanisms are illustrated through discussions of intracellular galectin assemblies in immune and cancer cells. This underscores the imperative need to fully comprehend the interplay of galectins with the cellular machinery and to devise therapeutic strategies aimed at counteracting the establishment of galectin-based disease mechanisms.

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Galectin-9 regulates dendritic cell polarity and uropod contraction by modulating RhoA activity

Franken,

Cuenca-Escalona,

Stehle

et al. 2023

Preprint

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To initiate adaptive immune responses, dendritic cells (DCs) migrate long distances to transport antigens from peripheral tissues to draining lymph nodes employing a so-called ameboid migration mode. Despite its critical importance, the specific molecular mechanisms that regulate DC migration are poorly characterised. Galectins, a family of β-galactoside-binding proteins, constitute a novel mechanism of membrane organisation at the cell surface and, in this way, exert crucial roles in multiple physiological and pathological processes. Nonetheless, the molecular mechanisms that underlie galectin functions are poorly described and their membrane interacting partners are mostly unknown.Here, we report that galectin-9 is required for the dynamic behaviour and motility of DCs. We demonstrate that galectin-9 deficiency results in impaired chemokine-driven and basal DC migration both in human and mouse, suggesting a conserved function for galectin-9. Deficiency in contractility was identified as the underlying mechanism, which could be rescued by restoring membrane-bound galectin-9 levels. Furthermore, we show that galectin-9 controls RhoA activity and downstream signalling, in turn causing rearrangements of the actin cytoskeleton at the cell rear that promote DC efficient migration. Galectin-9 interaction with the adhesion receptor CD44 was required for its function enhancing DC migration. Remarkably, analysis of DC motility in a 3D environment containing a tumour spheroid revealed galectin-9 is required for DC persistent migration towards the tumour and for DC infiltration. Moreover, exogenous galectin-9 rescued the motility of immunocompromised primary blood DCs, revealing a novel role for galectin-9 in the tumour microenvironment, with potential implications for DC-based immunotherapies.

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Galectin-9 interacts with Vamp-3 to regulate cytokine secretion in dendritic cells

Cited by 5 publications

References 63 publications

Natural Killer T Cell Diversity and Immunotherapy

Natural Killer T Cell Diversity and Immunotherapy

Intracellular galectin interactions in health and disease

Galectin-9 regulates dendritic cell polarity and uropod contraction by modulating RhoA activity

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