MHC II in Dendritic Cells is Targeted to Lysosomes or T Cell‐Induced Exosomes Via Distinct Multivesicular Body Pathways

Buschow, Sonja I.; Hoen, Esther N. M. Nolte‐‘t; Niel, Guillaume van; Pols, Maaike; Broeke, Toine ten; Lauwen, Marjolein M.; Ossendorp, Ferry; Melief, Cornelis J.M.; Raposo, Graça; Wubbolts, Richard; Wauben, Marca H. M.; Stoorvogel, Willem

doi:10.1111/j.1600-0854.2009.00963.x

Cited by 346 publications

(346 citation statements)

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“…In immature dendritic cells (DC), an alternative MVB sorting mechanism for MHC class II in antigens loaded DCs was observed in response to cognate interactions with T cells [17]. This pathway is characterized by the incorporation of MHC class II in detergentresistant protein complexes.…”

Section: Sorting By Protein Incorporation Into Detergent-resistant Prmentioning

confidence: 99%

“…MHC class II is sorted in MVB to ILVs for lysosomal targeting in a process that is driven by ubiquitination of the cytoplasmic domain of MHC class II. When DC interacts with a cognate T cell, ubiquitination is blocked and MHC class II is sorted together with CD9 into ILVs of the MVB resulting in secretion via exosomes [17]. Two distinct MVB pathways were characterized: one for lysosomal targeting and the other for exosome secretion.…”

Section: Sorting By Protein Incorporation Into Detergent-resistant Prmentioning

confidence: 99%

“…Exosomes secretion from immature dendritic cells (imDCs) can be transiently increased by T cell clones interaction or cognate CD4 + T cells [17,35]. Also Ag specific CD4 + T cells stimulates exosome release by activated B cells [41].…”

Section: Regulated Secretionmentioning

confidence: 99%

“…In each case a different subset of MVB would be involved, since exosome release is sectorized in the cell [80] and appearsnot involve all the MVBs. In that respect two distincts MVB pathways, one for lysosomal targeting and the other for exosome secretion have been characterized [17].…”

Section: Exosome Internalizationmentioning

confidence: 99%

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Exosomes as intercellular signalosomes and pharmacological effectors

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Silvente-Poirot

et al. 2011

Biochemical Pharmacology

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International audienceCell secretion is a general process involved in various biological responses. Exosomes are part of this process and have gained considerable scientific interest in the past five years. Several steps through investigations across the last 20years can explain this interest. First characterized during reticulocyte maturation, they were next characterized as a key player in the immune response and cancer immunotherapy. More recently they were characterized as vectors of mRNAs, miRNAs and also lipid mediators able to act on target cells. They are the only type of vesicles released from an intracellular compartment from cells in viable conditions. They appear as a vectorized signaling system operating from inside a donor cell towards either the periphery, the cytosol, or possibly to the nucleus of target cells. Exosomes from normal cells trigger positive effects, whereas those from pathological ones, such as tumor cells or infected ones may trigger non-positive health effects. Therefore regulating the biogenesis and secretion of exosomes appear as a pharmacological challenge to intervene in various pathophysiologies. Exosome biogenesis and molecular content, interaction with target cells, utilisation as biomarkers, and functional effects in various pathophysiologies are considered in this review

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Section: Sorting By Protein Incorporation Into Detergent-resistant Prmentioning

confidence: 99%

Section: Sorting By Protein Incorporation Into Detergent-resistant Prmentioning

confidence: 99%

Section: Regulated Secretionmentioning

confidence: 99%

Section: Exosome Internalizationmentioning

confidence: 99%

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Exosomes as intercellular signalosomes and pharmacological effectors

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Silvente-Poirot

et al. 2011

Biochemical Pharmacology

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“…Likewise, the melanosomal protein Pmel17 in melanoma cells 27 and major histocompatibility complex class II molecules in activated dendritic cells 28 are inserted into ILVs independently of ubiquitination. In addition, the CD63 itself is required for normal Pmel to be sorted into luminal domain in an ESCRT-independent manner 29 .…”

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confidence: 99%

Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes

et al. 2013

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During late endosome maturation, cargo molecules are sorted into intralumenal vesicles (ILVs) of multivesicular endosomes (MVEs), and are either delivered to lysosomes for degradation or fused with the plasma membranes for exosome release. The mechanism underlying formation of exosomal ILVs and cargo sorting into ILVs destined for exosome release is still unclear. Here we show that inhibitory G protein (Gi)-coupled sphingosine 1-phosphate (S1P) receptors regulate exosomal MVE maturation. Gi-coupled S1P receptors on MVEs are constitutively activated through a constant supply of S1P via autocrine activation within organelles. We also found that the continuous activation of Gi-coupled S1P receptors on MVEs is essential for cargo sorting into ILVs destined for exosome release. Our results reveal a mechanism underlying ESCRT-independent maturation of exosomal MVEs.

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Exosomes: The Indispensable Messenger in Tumor Pathogenesis and the Rising Star in Antitumor Applications

Wang

Wei

et al. 2019

Adv. Biosys.

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understanding of the underlying interaction mechanisms between tumor cells and the TME, as well as derivative tumor treatment strategies, is of great significance for oncology and diagnostic development.Exosomes represent a kind of nanosized (30-150 nm) lipid bilayer membrane vesicles that are naturally secreted by almost all types of cells and exist widely in various body fluids, such as plasma, [4] saliva, [5] perspiration, urine, [6] latex, cerebrospinal fluid, nasal mucus, and ascites. After their discovery in 1983, exosomes were widely considered as useless "cellular waste" for a long time. [7] In 1996, Raposo et. al. [8] demonstrated that exosomes derived from human and murine B lymphocytes could transfer antigen and induce antigen-specific T cell responses, which discovery changed the "cellular waste concept" of exosomes. Renewed interest in exosomes followed recent reports demonstrating that exosomes contribute to various aspects of cellular homeostasis, physiology and pathobiology. [9] Intercellular communication is considered as one of the most fascinating roles of exosomes. [10] As the intercellular vehicles to transport message, exosomes inherit various molecular information (including proteins, nucleic acids, lipids) from the origin cell and reflect the phenotypic state. Moreover, these biological entities subsequently affect physiological and pathological processes such as inflammation, immune surveillance, tumorigenesis. [11] As important parts of the tumor microenvironment (TME), exosomes have been widely investigated in past decades and demonstrated to possess specialized functions in tumor initiation, progression, metastasis, angiogenesis, and drug resistance. [12,13] Moreover, the specific molecular signature inherited from the origin tumor cell endow tumor-derived exosomes with the capacity to predict tumor progression and prognosis. [14,15] On the other hand, immune cell-derived exosomes, such as DC-derived exosomes, NK-derived exosomes and M1 macrophage-derived exosomes, play vital roles in activating antitumor immune response, which properties endow these exosomes with promising potential in acting as tumor therapeutic vaccine. In addition, the vesicular biocompatibility, nanometer dimension size and biochemical properties make sophisticated exosomes a novel promising therapeutic nanoplatform in cancer. [16] In this review, efforts are made to provide a comprehensive and critical overview about recent advances in exosome-related research field, ranging from their biogenesis, secretion, isolation and biological function in tumor pathogenesis to their extensive antitumor applications.As natural secreted nanovesicles through the endolysosomal pathway, exosomes have attracted increasing attention over the past decades. An overwhelming number of studies have provided evidence for the intriguing roles that exosomes play in intercellular communication. They are widely involved in the transmission of biomolecule cargos between original cells and neighboring/distant cells in normal physiologica...

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MHC II in Dendritic Cells is Targeted to Lysosomes or T Cell‐Induced Exosomes Via Distinct Multivesicular Body Pathways

Abstract: † These authors contributed equally to this work.

Cited by 346 publications

References 66 publications

Exosomes as intercellular signalosomes and pharmacological effectors

Exosomes as intercellular signalosomes and pharmacological effectors

Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes

Exosomes: The Indispensable Messenger in Tumor Pathogenesis and the Rising Star in Antitumor Applications

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