Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Exosomes are extracellular vesicles (EV) of endosomal origin (multivesicular bodies, MVB) constitutively released by many different eukaryotic cells by fusion of MVB to the plasma membrane. However, inducible exosome secretion controlled by cell surface receptors is restricted to very few cell types and a limited number of cell surface receptors. Among these, exosome secretion is induced in T lymphocytes and B lymphocytes when stimulated at the immune synapse (IS) via T-cell receptors (TCR) and B-cell receptors (BCR), respectively. IS formation by T and B lymphocytes constitutes a crucial event involved in antigen-specific, cellular, and humoral immune responses. Upon IS formation by T and B lymphocytes with antigen-presenting cells (APC), the convergence of MVB towards the microtubule organization center (MTOC), and MTOC polarization to the IS, are involved in polarized exosome secretion at the synaptic cleft. This specialized mechanism provides the immune system with a finely-tuned strategy to increase the specificity and efficiency of crucial secretory effector functions of B and T lymphocytes. As inducible exosome secretion by antigen-receptors is a critical and unique feature of the immune system this review considers the study of the traffic events leading to polarized exosome secretion at the IS and some of their biological consequences.

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Cell Surface Receptors: Rapid Quantification of Live Cell Receptors Using Bioluminescence in a Flow-Based Microfluidic Device (Small 8/2015)

Small ◽

10.1002/smll.201570050 ◽

2015 ◽

Vol 11 (8) ◽

pp. 1012-1012

Author(s):

Ramesh Ramji ◽

Cheong Fook Cheong ◽

Hiroaki Hirata ◽

Abdur Rub Abdur Rahman ◽

Chwee Teck Lim

Keyword(s):

Cell Surface ◽

Microfluidic Device ◽

Live Cell ◽

Cell Surface Receptors ◽

Cell Receptors ◽

Surface Receptors ◽

Rapid Quantification

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Reduction of leucocyte cell surface disulfide bonds during immune activation is dynamic as revealed by a quantitative proteomics workflow (SH-IQ)

Open Biology ◽

10.1098/rsob.180079 ◽

2018 ◽

Vol 8 (9) ◽

pp. 180079

Author(s):

Monika Stegmann ◽

A. Neil Barclay ◽

Clive Metcalfe

Keyword(s):

Immune System ◽

Cell Surface ◽

Immune Activation ◽

Disulfide Bonds ◽

Cell Function ◽

Immune Cell ◽

Surface Proteins ◽

Cell Surface Receptors ◽

Surface Receptors ◽

Pathogen Clearance

Communication through cell surface receptors is crucial for maintaining immune homeostasis, coordinating the immune response and pathogen clearance. This is dependent on the interaction of cell surface receptors with their ligands and requires functionally active conformational states. Thus, immune cell function can be controlled by modulating the structure of either the receptor or the ligand. Reductive cleavage of labile disulfide bonds can mediate such an allosteric change, resulting in modulation of the immune system by a hitherto little studied mechanism. Identifying proteins with labile disulfide bonds and determining the extent of reduction is crucial in elucidating the functional result of reduction. We describe a mass spectrometry-based method—thiol identification and quantitation (SH-IQ)—to identify, quantify and monitor such reduction of labile disulfide bonds in primary cells during immune activation. These results provide the first insight into the extent and dynamics of labile disulfide bond reduction in leucocyte cell surface proteins upon immune activation. We show that this process is thiol oxidoreductase-dependent and mainly affects activatory (e.g. CD132, SLAMF1) and adhesion (CD44, ICAM1) molecules, suggesting a mechanism to prevent over-activation of the immune system and excessive accumulation of leucocytes at sites of inflammation.

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Multiple Targets for Oxysterols in Their Regulation of the Immune System

Cells ◽

10.3390/cells10082078 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2078

Author(s):

Lisa Reinmuth ◽

Cheng-Chih Hsiao ◽

Jörg Hamann ◽

Mette Rosenkilde ◽

John Mackrill

Keyword(s):

Immune System ◽

Cell Surface ◽

Oxidation Products ◽

Epigenetic Mechanism ◽

Cell Surface Receptor ◽

Cholesterol Oxidation ◽

Cell Surface Receptors ◽

Cholesterol Oxidation Products ◽

Surface Receptors ◽

Cellular Processes

Oxysterols, or cholesterol oxidation products, are naturally occurring lipids which regulate the physiology of cells, including those of the immune system. In contrast to effects that are mediated through nuclear receptors or by epigenetic mechanism, which take tens of minutes to occur, changes in the activities of cell-surface receptors caused by oxysterols can be extremely rapid, often taking place within subsecond timescales. Such cell-surface receptor effects of oxysterols allow for the regulation of fast cellular processes, such as motility, secretion and endocytosis. These cellular processes play critical roles in both the innate and adaptive immune systems. This review will survey the two broad classes of cell-surface receptors for oxysterols (G-protein coupled receptors (GPCRs) and ion channels), the mechanisms by which cholesterol oxidation products act on them, and their presence and functions in the different cell types of the immune system. Overall, this review will highlight the potential of oxysterols, synthetic derivatives and their receptors for physiological and therapeutic modulation of the immune system.

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The condition of piglet immune system during post-weaning period depending on the sex and stress-reactivity

Innovations and Food Safety ◽

10.31677/2072-6724-2021-31-1-98-105 ◽

2021 ◽

pp. 98-105

Author(s):

N. V. Efanova ◽

V. V. Gart ◽

К. V. Zhuchaev ◽

L. M. Osina ◽

S. V. Batalova

Keyword(s):

T Cells ◽

Immune System ◽

T Lymphocytes ◽

B Lymphocytes ◽

Stress Reactivity ◽

Helper T Cells ◽

T And B Lymphocytes ◽

Antibody Synthesis ◽

Igg Synthesis ◽

High Proliferative Activity

The immune system of 90-day old piglets of SM-1 Novosibirsk breed piglets depends on sex and stress-reactivity. Stress-reactivity was measured using halothane test. The immunologic testing was performed 30 days after weaning. Our results show that overall piglet immune system demonstrated high proliferative activity of T- and B- immunocompetent cells with active formation of mature active T-and B-lymphocytes and did not show signs of immunosuppression. Compared to guilts, barrows had higher concentration of leucocytes, T-and B-lymphocytes, killer-supressor T-cells, activated and poorly differentiated T-lymphocytes. Gilts had higher production of inductor-helper T-cells, IgM and IgG when compared to barrows. Stress-resistant piglets had higher concentration of B-lymphocytes, IgM and IgG whereas stress-sensitive piglets had higher concentration of T-lymphocytes, supressor-killer T-cells and thymus T-lymphocytes. Gilts had higher concentration of inductor-helper T-cells than killer-supressor T-cells. Gilts overall had intensive antibody synthesis, however, stress-resistant gilts had higher IgG synthesis compared to stress-sensitive gilts. In barrows immature T-lymphocytes differentiated mainly into killer-supressor T-cells. The adaptivity of barrow immune system was characterized by high circulatory B-lymphocytes and IgM. Stress-sensitive barrows had lower antibody synthesis levels and higher T-lymphophoesis compared to stress-resistant barrows.

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