Role of Exosomes in the Regulation of T-Cell Mediated Immune Responses and in Autoimmune Disease

Anel, Alberto; Gallego-Lleyda, Ana; Miguel, Diego de; Naval, Javier; Martínez-Lostao, Luis

doi:10.3390/cells8020154

Cited by 130 publications

(94 citation statements)

References 139 publications

(148 reference statements)

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“…Thus it was hypothesized that exosomes may be useful for the treatment of certain autoimmune diseases [118,119]. In this context, Treg-derived exosomes have been shown to inhibit the development of murine arthritis and to prevent certain autoimmune diseases [128]. The clinical value of Treg-derived exosomes has been extensively discussed in several recent reviews [128,129].…”

Section: Role Of T Lymphocyte-produced Exosomes On Apoptosis and Immumentioning

confidence: 99%

Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Calvo

Izquierdo

2020

IJMS

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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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Section: Role Of T Lymphocyte-produced Exosomes On Apoptosis and Immumentioning

confidence: 99%

Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Calvo

Izquierdo

2020

IJMS

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“…EVs derived from cancer cells harbor numerous cancer-related molecules that can promote cell transformation, tumor growth, and cell invasion [ 128 , 129 , 130 ]. In addition, EVs derived from cancer cells can inhibit anti-tumor T-cell responses by inducing FasL, TRAIL, and PDL-2-related apoptosis [ 131 ] Carefully choosing EV-producing cell lines and strictly controlling their composition are instrumental for ensuring the safety of EV nanotherapeutics. Stem cells such as MSCs, although they do not undergo malignant transformation during long-term passaging [ 132 ], still accrue mutations [ 133 ].…”

Section: Extracellular Vesicles (Ev) As Drug Delivery Vehiclesmentioning

confidence: 99%

Gene Editing by Extracellular Vesicles

Kostyushev

Kostyusheva

Brezgin

et al. 2020

IJMS

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CRISPR/Cas technologies have advanced dramatically in recent years. Many different systems with new properties have been characterized and a plethora of hybrid CRISPR/Cas systems able to modify the epigenome, regulate transcription, and correct mutations in DNA and RNA have been devised. However, practical application of CRISPR/Cas systems is severely limited by the lack of effective delivery tools. In this review, recent advances in developing vehicles for the delivery of CRISPR/Cas in the form of ribonucleoprotein complexes are outlined. Most importantly, we emphasize the use of extracellular vesicles (EVs) for CRISPR/Cas delivery and describe their unique properties: biocompatibility, safety, capacity for rational design, and ability to cross biological barriers. Available molecular tools that enable loading of desired protein and/or RNA cargo into the vesicles in a controllable manner and shape the surface of EVs for targeted delivery into specific tissues (e.g., using targeting ligands, peptides, or nanobodies) are discussed. Opportunities for both endogenous (intracellular production of CRISPR/Cas) and exogenous (post-production) loading of EVs are presented.

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“…Exosomes are membrane -bound extracellular vesicles with key roles in intercellular communication and transport. Exosome exchange can regulate CD8 + T cell function and communication with other immune and tumour cells in the tumour microenvironment 28,29 .…”

Section: Click-proteomics Reveals P5 Interactions With Cellular Transmentioning

confidence: 99%

CLICK-enabled analogues reveal pregnenolone interactomes in cancer and immune cells

Roy

Sipthorp²,

Mahata

et al. 2019

Preprint

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Pregnenolone (P5) promotes prostate cancer cell growth, and de novo synthesis of intratumoural P5 is a potential cause of development of castration-resistance. Immune cells can also synthesize P5 de novo. Despite its biological importance, little is known about P5's mode of actions, which appears to be context-dependent and pleiotropic. A comprehensive proteome-wide spectrum of P5-binding proteins that are involved in its trafficking and functionality remains unknown. Here, we describe an approach that integrates chemical biology for probe synthesis with chemoproteomics to map P5protein interactions in live prostate cancer cells and murine CD8 + T cells. We subsequently identified P5-binding proteins potentially involved in P5-trafficking, and in P5's non-genomic action that may drive the promotion of castrate-resistance prostate cancer and regulate CD8 + T cell function. We envisage that this methodology could be employed for other steroids to map their interactomes directly in a broad range of living cells, tissues and organisms.glioma it restricts tumour growth 11 . The mode-of-action of P5 in tumours is incompletely understood. In the nervous system, P5 is known to regulate synapse formation, outgrowth of neurites and enhances myelinization 12 , improves cognitive and memory function 13 .During immune response against helminth parasite infection T helper cells synthesize P5 to restore immune homeostasis 4 . Up to now, we do not have a proteome-wide description of the P5-interacting molecules in any living cells.Traditionally, steroid hormones have been considered to act by regulating transcription 14 . However, rapid activity of steroid hormones can be mediated by nongenomic pathways 15 . Non-genomic pathways appear to mediate P5 activity 16 in a cell type-specific and context-dependent manner, indicating a need for proteome-wide studies to map the full spectrum of P5 functions.Here, we have developed a chemical biology method to generate clickable P5analogues for use in living cells. Exploiting these P5-probes in combination with quantitative mass-spectrometry, we profiled global P5-protein interactions directly in two distinct cell types: a steroid-sensitive cell line derived from a metastatic prostate cancer patient (i.e. LNCaP) and de novo P5-producing mouse CD8 + T cells.Altogether, we identified 62 high-confidence P5 binding and about 387 potential P5binding proteins localized in the nucleus, mitochondria and endoplasmic reticulum.These proteins include receptors, channels, transporters, cytoskeletal proteins such as vimentin and enzymes, of which many represent novel interactions. Overall, we identified P5-binding proteins potentially involved in inter-and intra-cellular P5trafficking and P5's non-genomic action that drives prostate cancer promotion of castration-resistance, and mediates CD8 + T cell regulation.

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Role of Exosomes in the Regulation of T-Cell Mediated Immune Responses and in Autoimmune Disease

Cited by 130 publications

References 139 publications

Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Gene Editing by Extracellular Vesicles

CLICK-enabled analogues reveal pregnenolone interactomes in cancer and immune cells

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