High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites

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Intracellular Galectin-9 Controls Dendritic Cell Function by Maintaining Plasma Membrane Rigidity

Biological Sciences; Molecular Biology; Cell BiologyEndogenous extracellular Galectins constitute a novel mechanism of membrane protein organization at the cell surface. Although Galectins are also highly expressed intracellularly, their cytosolic functions are poorly understood. Here, we investigated the role of Galectin-9 in dendritic cell (DC) surface organization and function. By combining functional, super-resolution and atomic force microscopy experiments to analyze membrane stiffness, we identified intracellular Galectin-9 to be indispensable for plasma membrane integrity and structure in DCs. Galectin-9 knockdown studies revealed intracellular Galectin-9 to directly control cortical membrane structure by modulating Rac1 activity, providing the underlying mechanism of Galectin-9-dependent actin cytoskeleton organization. Consequent to its role in maintaining plasma membrane structure, phagocytosis studies revealed that Galectin-9 was essential for C-type-lectin receptor-mediated pathogen uptake by DCs. This was confirmed by the impaired phagocytic capacity of Galectin-9-null murine DCs. Together, this study demonstrates a novel role for intracellular Galectin-9 in modulating DC function, which may be evolutionarily conserved

Tetraspanins in the humoral immune response.

Contains fulltext : 97406pub.pdf (publisher's version ) (Closed access)The tetraspanins represent a large superfamily of four-transmembrane proteins that are expressed on all nucleated cells. Tetraspanins play a prominent role in the organization of the plasma membrane by co-ordinating the spatial localization of transmembrane proteins and signalling molecules into 'tetraspanin microdomains'. In immune cells, tetraspanins interact with key leucocyte receptors [including MHC molecules, integrins, CD4/CD8 and the BCR (B-cell receptor) complex] and as such can modulate leucocyte receptor activation and downstream signalling pathways. There is now ample evidence that tetraspanins on B-lymphocytes are important in controlling antibody production. The tetraspanin CD81 interacts with the BCR complex and is critical for CD19 expression and IgG production, whereas the tetraspanin CD37 inhibits IgA production and is important for IgG production. By contrast, the tetraspanins CD9, Tssc6 and CD151 appear dispensable for humoral immune responses. Thus individual tetraspanin family members have specific functions in B-cell biology, which is evidenced by recent studies in tetraspanin-deficient mice and humans. The present review focuses on tetraspanins expressed by B-lymphocytes and discusses novel insights into the function of tetraspanins in the humoral immune response.1 april 201

Fungal pattern-recognition receptors and tetraspanins: partners on antigen-presenting cells.

Contains fulltext : 88560.pdf (publisher's version ) (Closed access)Fungal pattern-recognition receptors (F-PRRs), including C-type lectins, Toll-like receptors, scavenger receptors and Fc/complement receptors, are crucial for inducing anti-fungal immune responses by antigen-presenting cells. The recent identification of specific F-PRR interactions with tetraspanins has shed new light on the functioning of F-PRRs in the cell membrane and subsequent downstream signaling. Tetraspanins are small four-transmembrane proteins that can assemble immune receptors and signaling molecules into functional membrane microdomains. Here, we discuss the implications of this novel type of interaction between F-PRRs and tetraspanins in different subsets of antigen-presenting cells. We postulate that upon fungal binding tetraspanins modulate the function of F-PRRs by their recruitment into tetraspanin microdomains, leading to immune activation or tolerance.1 maart 201

Editorial: Membrane domains as new drug targets

Contains fulltext : 155114.pdf (publisher's version ) (Open Access

Antitumor Immunity Is Controlled by Tetraspanin Proteins

Contains fulltext : 200585.pdf (publisher's version ) (Open Access)Antitumor immunity is shaped by the different types of immune cells that are present in the tumor microenvironment (TME). In particular, environmental signals (for instance, soluble factors or cell-cell contact) transmitted through the plasma membrane determine whether immune cells are activated or inhibited. Tetraspanin proteins are emerging as central building blocks of the plasma membrane by their capacity to cluster immune receptors, enzymes, and signaling molecules into the tetraspanin web. Whereas some tetraspanins (CD81, CD151, CD9) are widely and broadly expressed, others (CD53, CD37, Tssc6) have an expression pattern restricted to hematopoietic cells. Studies using genetic mouse models have identified important immunological functions of these tetraspanins on different leukocyte subsets, and as such, may be involved in the immune response against tumors. While multiple studies have been performed with regards to deciphering the function of tetraspanins on cancer cells, the effect of tetraspanins on immune cells in the antitumor response remains understudied. In this review, we will focus on tetraspanins expressed by immune cells and discuss their potential role in antitumor immunity. New insights in tetraspanin function in the TME and possible prognostic and therapeutic roles of tetraspanins will be discussed

The role of tetraspanins in the pathogenesis of infectious diseases.

Contains fulltext : 87727.pdf (publisher's version ) (Closed access)Tetraspanin proteins on host cells are involved in the pathogenesis of infectious diseases at different stages. In this review, we will focus on tetraspanins expressed in the immune system and the role they play in the defense to viral, bacterial, parasitic and fungal infections.1 februari 201

The fat and the furious: fatty acids fuel hyperproliferative germinal center B cells

Contains fulltext : 229335.pdf (Publisher’s version ) (Closed access

Tetraspanins in the immune response against cancer

Contains fulltext : 97407.pdf (publisher's version ) (Closed access)The role of the immune system in the defense against cancer, a process termed tumor immunosurveillance, has been extensively studied. Evidence is accumulating that the molecular organization of proteins and lipids in the plasma membrane of immune cells is of critical importance. Tetraspanin proteins are expressed in the plasma membrane of all mammalian cells and play an important role in the spatial organization of partner molecules into tetraspanin-enriched microdomains. It is now well established that tetraspanins interact with one another as well as with a diverse array of key leukocyte proteins, including immune receptors, integrins, and signaling molecules. These tetraspanin-partner protein interactions control several fundamental cellular processes, which in immune cells involve antigen presentation, motility, proliferation and antibody production. We propose that differences in the tetraspanin microdomain composition account for the abilities of individual tetraspanins to either promote or suppress immune responses. In this review, we discuss novel insights into tetraspanin function in immune cells, and describe how this may control anti-tumor immunity