Dendritic Cells Release HLA-B-Associated Transcript-3 Positive Exosomes to Regulate Natural Killer Function

Simhadri, Venkateswara R.; Reiners, Katrin S.; Hansen, Hinrich P.; Topolar, Daniela; Simhadri, Vijaya L.; Nohroudi, Klaus; Kufer, Thomas A.; Engert, Andreas; Strandmann, Elke Pogge von

doi:10.1371/journal.pone.0003377

Cited by 214 publications

(193 citation statements)

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“…Dendritic cells derived exosomes were also shown to regulate NK cells functions, such as inflammatory -B associated transcript-3 (BAT3) expressed on their surface [89]. This intracellular protein which is involved in DNA damageinduced apoptosis represents the ligand for a natural cytotoxicity receptor expressed on NK cell, the NKp30, involved in direct cytotoxicity against tumor cells.…”

Section: Stimulation Of Immunocompetent Cellsmentioning

confidence: 99%

Exosomes as intercellular signalosomes and pharmacological effectors

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Silvente-Poirot

et al. 2011

Biochemical Pharmacology

475

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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: Stimulation Of Immunocompetent Cellsmentioning

confidence: 99%

Exosomes as intercellular signalosomes and pharmacological effectors

Record

Subra

Silvente-Poirot

et al. 2011

Biochemical Pharmacology

475

336

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“…29,30 NKp30 triggers cytotoxicity and cytokine release upon binding B7H6 or BAT3 at the cell surface. 24,25,31 Besides NCRs, other activating receptors, including NKG2D and DNAM-1, contribute to trigger the NK cell-mediated cytotoxicity. 32-34 Ligands specific for these receptors have been extensively characterized: MICA/B and ULBPs molecules are recognized by NKG2D, while PVR and Nectin-2 (belonging to the Nectin family), are ligands for DNAM-1.…”

Section: Introductionmentioning

confidence: 99%

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

et al. 2018

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The release of soluble ligands of activating Natural Killer (NK) cell receptors may represent a regulatory mechanism of NK cell function both in physiologic and in pathologic conditions. Here, we identified the extracellular matrix protein Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed by activated NK cells. When released as soluble molecule, NID1 regulates NK cell function by modulating NKp44-induced IFN-γ production or cytotoxicity. In particular, it also modulates IFN-γ production induced by Platelet-Derived Growth Factor (PDGF)-DD following NKp44 engagement. We also show that NID1 may be present at the cell surface. In this form or when bound to a solid support (bNID1), NID1 fails to induce NK cell cytotoxicity or cytokine release. However, analysis by mass spectrometry revealed that exposure to bNID1 can induce in human NK cells relevant changes in the proteomic profiles suggesting an effect on different biological processes.

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“…NKp30-specific cellular ligands that are expressed at the cell surface or released on exosomes include the HLA-B-associated transcript 3 (16,18) and the most recently identified B7-H6 (15,19,20). Whereas HLA-B-associated transcript 3 has been reported to be expressed by both malignant and healthy cells such as dendritic cells (16,18), B7-H6 to date has not been found on normal cells, suggesting that this ligand may be exclusively displayed by aberrant cells and to be absent from healthy tissues (15,21).…”

mentioning

confidence: 99%

“…Whereas HLA-B-associated transcript 3 has been reported to be expressed by both malignant and healthy cells such as dendritic cells (16,18), B7-H6 to date has not been found on normal cells, suggesting that this ligand may be exclusively displayed by aberrant cells and to be absent from healthy tissues (15,21). The ligand B7-H6 belongs to the B7 molecule family comprising several members that exert both immune stimulatory and inhibitory functions (22).…”

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confidence: 99%

Mimicking an Induced Self Phenotype by Coating Lymphomas with the NKp30 Ligand B7-H6 Promotes NK Cell Cytotoxicity

Kellner

Maurer

Hallack

et al. 2012

The Journal of Immunology

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Induced self expression of the NKp30 ligand B7-H6 facilitates NK cell-mediated elimination of stressed cells. A fusion protein consisting of the ectodomain of B7-H6 and the CD20 single-chain fragment variable 7D8 was generated to mimic an induced self phenotype required for NK cell-mediated target cell elimination. B7-H6:7D8 had bifunctional properties as reflected by its ability to simultaneously bind to the CD20 Ag and to the NKp30 receptor. B7-H6:7D8 bound by CD20+ lymphoma cells activated human NK cells and triggered degranulation. Consequently, the immunoligand B7-H6:7D8 induced killing of lymphoma-derived cell lines as well as fresh tumor cells from chronic lymphocytic leukemia or lymphoma patients. B7-H6:7D8 was active at nanomolar concentrations in a strictly Ag-specific manner and required interaction with both CD20 and NKp30. Remarkably, NK cell cytotoxicity was further augmented by concomitant activation of Fcγ receptor IIIa or NK group 2 member D. Thus, B7-H6:7D8 acted synergistically with the CD20 Ab rituximab and the immunoligand ULBP2:7D8, which was similarly designed as B7-H6:7D8 but engaging the NK group 2 member D receptor. In conclusion, to our knowledge, B7-H6:7D8 represents the first Ab-based molecule stimulating NKp30-mediated NK cell cytotoxicity for therapeutic purposes and provides proof of concept that Ag-specific NKp30 engagement may represent an innovative strategy to enhance antitumoral NK cell cytotoxicity.

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Dendritic Cells Release HLA-B-Associated Transcript-3 Positive Exosomes to Regulate Natural Killer Function

Cited by 214 publications

References 40 publications

Exosomes as intercellular signalosomes and pharmacological effectors

Exosomes as intercellular signalosomes and pharmacological effectors

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

Mimicking an Induced Self Phenotype by Coating Lymphomas with the NKp30 Ligand B7-H6 Promotes NK Cell Cytotoxicity

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