Role of ERM (ezrin-radixin-moesin) proteins in T lymphocyte polarization, immune synapse formation and in T cell receptor-mediated signaling

AbstractBy hydrolyzing its substrate sphingomyelin at the cytosolic leaflet of cellular membranes, the neutral sphingomyelinase 2 (NSM2) generates microdomains which serve as docking sites for signaling proteins and thereby, functions to regulate signal relay. This has been particularly studied in cellular stress responses while the regulatory role of this enzyme in the immune cell compartment has only recently emerged. In T cells, phenotypic polarization by co-ordinated cytoskeletal remodeling is central to motility and interaction with endothelial or antigen-presenting cells during tissue recruitment or immune synapse formation, respectively. This review highlights studies adressing the role of NSM2 in T cell polarity in which the enzyme plays a major role in regulating cytoskeletal dynamics.

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Searching for immunotherapeutic targets in oncology during immune synapse formation

Problems in oncology ◽

10.37469/0507-3758-2021-67-3-344-349 ◽

2021 ◽

Vol 67 (3) ◽

pp. 344-349

Author(s):

Tatiana Nehaeva ◽

Artem Karpov ◽

Nino Pipia

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Synapse Formation ◽

Immunological Synapse ◽

Cell Receptor ◽

Ligand Molecule ◽

Receptor Ligands ◽

Immune Synapse ◽

Central Cluster ◽

Antigen Presenting

Immunological synapse (IS) is a high-specialized connection between a T-lymphocyte and an antigen-presenting cell (APC), consisting of a cluster of T-cell receptors (TCR) surrounded by a ring of adhesion molecules. It has now been shown that formation of immune synapses is an active and dynamic mechanism that allows T cells to discriminate between potential antigenic ligands. At the first stage T-cell receptor ligands are involved in the external ring of the forming synapse. The movement of these complexes into the central cluster depends on the kinetics of T-cell receptor-ligand molecule interaction. Thus, the formation of a stable central cluster in the immunological synapse is a determining event for T-cell proliferation. The application of effective ways to influence on the IS by introduction into practice of new antitumor drugs and immunological synapse modulators allows to take a new look at the possibilities of tumor immunotherapy.

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Dynein-Driven Transport of T Cell Receptor Microclusters Regulates Immune Synapse Formation and T Cell Activation

Immunity ◽

10.1016/j.immuni.2011.05.012 ◽

2011 ◽

Vol 34 (6) ◽

pp. 919-931 ◽

Cited By ~ 107

Author(s):

Akiko Hashimoto-Tane ◽

Tadashi Yokosuka ◽

Kumiko Sakata-Sogawa ◽

Machie Sakuma ◽

Chitose Ishihara ◽

...

Keyword(s):

T Cell ◽

T Cell Receptor ◽

T Cell Activation ◽

Cell Activation ◽

Synapse Formation ◽

Cell Receptor ◽

Immune Synapse

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Faculty Opinions recommendation of T cell receptor signaling precedes immunological synapse formation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1004974.58104 ◽

2002 ◽

Author(s):

Andre Veillette

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Synapse Formation ◽

Immunological Synapse ◽

Cell Receptor ◽

Receptor Signaling ◽

T Cell Receptor Signaling ◽

Cell Receptor Signaling

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Faculty Opinions recommendation of Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1098808.554944 ◽

2008 ◽

Author(s):

Deborah Leckband

Keyword(s):

T Cells ◽

T Cell ◽

Adhesion Molecules ◽

T Cell Receptor ◽

Synapse Formation ◽

Immunological Synapse ◽

Cell Receptor ◽

Jurkat T Cells

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Ceramide Synthase 2 Null Mice Are Protected from Ovalbumin-Induced Asthma with Higher T Cell Receptor Signal Strength in CD4+ T Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22052713 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2713

Author(s):

Sun-Hye Shin ◽

Kyung-Ah Cho ◽

Hee-Soo Yoon ◽

So-Yeon Kim ◽

Hee-Yeon Kim ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Receptor ◽

Cd4 T Cells ◽

Acyl Chain ◽

Signal Strength ◽

Cell Receptor ◽

Ceramide Synthase ◽

Asthmatic Patients

(1) Background: six mammalian ceramide synthases (CerS1–6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murine allergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22–C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice. (2) Methods: asthma was induced in wild type (WT) and CerS2 null mice with ovalbumin (OVA), and inflammatory cytokines and CD4 (cluster of differentiation 4)+ T helper (Th) cell profiles were analyzed. We also compared the functional capacity of CD4+ T cells isolated from WT and CerS2 null mice. (3) Results: CerS2 null mice exhibited milder symptoms and lower Th2 responses than WT mice after OVA exposure. CerS2 null CD4+ T cells showed impaired Th2 and increased Th17 responses with concomitant higher T cell receptor (TCR) signal strength after TCR stimulation. Notably, increased Th17 responses of CerS2 null CD4+ T cells appeared only in TCR-mediated, but not in TCR-independent, treatment. (4) Conclusions: altered Th2/Th17 immune response with higher TCR signal strength was observed in CerS2 null CD4+ T cells upon TCR stimulation. CerS2 and very-long chain SLs may be therapeutic targets for Th2-related diseases such as asthma.

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