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1.

001-es BibID:BIBFORM065606
Első szerző:Fekete Tünde (immunológus, molekuláris biológus, mikrobiológus)
Cím:Interferon gamma boosts the nucleotide oligomerization domain 2-mediated signaling pathway in human dendritic cells in an X-linked inhibitor of apoptosis protein and mammalian target of rapamycin-dependent manner / Tünde Fekete, Gabor Koncz, Brigitta Szabo, Andrea Gregus, Eva Rajnavölgyi
Dátum:2017
ISSN:1672-7681 2042-0226
Megjegyzések:The cytoplasmic nucleotide oligomerization domain 2 (NOD2) receptor recognizes the bacterial cell wall componentmuramyl dipeptide (MDP). NOD2 ligation initiates the nuclear factor kappa B and the mitogen-activated protein kinasecascades. However, administering MDP alone is insufficient to elicit strong cytokine responses in various immune cells,including dendritic cells (DCs). Because the simultaneous presence of various microbial products and cytokines ininflamed tissues modulates DC function, we initiated this study to examine how interferon gamma (IFNc), a centralmodulator of inflammation, affects the NOD2-mediated signaling pathway in human conventional DCs (cDCs).Synergistic stimulation of DCs with MDP and IFNc increased the expression of CD40, CD80, CD83, CD86, and humanleukocyte antigen DQ proteins and significantly elevated the production of pro-inflammatory cytokines IL-1b, IL-6, IL-12,and tumour necrosis factor (TNF), as well as anti-inflammatory cytokine IL-10. Furthermore, the simultaneous presenceofMDP and IFNc was necessary to decrease IkBa protein levels. By investigating various mechanisms implicated in MDPandIFNc-mediated signaling pathways, we revealed that the increased production of pro-inflammatory cytokines ishighly dependent on the X-linked inhibitor of apoptosis protein (XIAP) but not on cellular IAP1 and IAP2. We also foundthat the NOD2 signaling pathway is regulated by the mammalian target of rapamycin (mTOR) but is not affected byphosphatidylinositol-3 kinase or signal transducer and activator of transcription 1 inhibition. Our results demonstrate, forthe first time, that IFNc positively affects NOD2-mediated signaling in human cDCs, in a manner considerably dependenton XIAP and partially dependent on mTOR.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
dendritic cell
mTOR
NOD2
XIAP
Megjelenés:Cellular And Molecular Immunology 14 : 4 (2017), p. 380-391. -
További szerzők:Koncz Gábor (1970-) (biológus, immunológus) Szabó Brigitta Gregus Andrea (1980-) (biológus) Rajnavölgyi Éva (1950-) (immunológus)
Pályázati támogatás:NN114423
OTKA
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2.

001-es BibID:BIBFORM053804
Első szerző:Fekete Tünde (immunológus, molekuláris biológus, mikrobiológus)
Cím:The antiviral immune response in human conventional dendritic cells is controlled by the mammalian target of rapamycin / Tünde Fekete, Kitti Pazmandi, Attila Szabo, Attila Bacsi, Gabor Koncz, Eva Rajnavölgyi
Dátum:2014
ISSN:0741-5400
Megjegyzések:Type I and III IFNs are crucial, soluble components of potent antiviral responses. It has been explored recently that mTOR is involved in the regulation of IFN-?/? production by pDCs, albeit its role in the induction of IFN responses in cDCs remained unrevealed. In this study, we demonstrate that the PI3K/mTOR pathway is indispensable for eliciting intact type I and III IFN responses in moDCs stimulated with polyI:C. The inhibition of mTOR functionality by rapamycin impairs the pIRF3 and also a few members of the MAPK family, suggesting that mTOR contributes to the activation of multiple signaling pathways in the presence of viral antigens. Furthermore, rapamycin-treated moDCs show decreased capacity to prime IFN-? secretion by naive CD8+ T-lymphocytes. As in moDCs, mTOR-mediated regulation is also essential for the production of type I and III IFNs in circulating CD1c+ DCs. To our best knowledge, these results demonstrate for the first time that mTOR has an impact on the functional activities of cDCs via modulating the outcome of IFN secretion.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
dendritic cell
Megjelenés:Journal of Leukocyte Biology. - 96 (2014), p. 1-11. -
További szerzők:Pázmándi Kitti Linda (1984-) (molekuláris biológus, immunológus) Szabó Attila (1981-) (molekuláris biológus, immunológus, filozófus) Bácsi Attila (1967-) (immunológus) Koncz Gábor (1970-) (biológus, immunológus) Rajnavölgyi Éva (1950-) (immunológus)
Pályázati támogatás:4.2.2.A-11/1/KONV- 2012-0023 "VÉD-ELEM"
TÁMOP
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Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM072879
Első szerző:Hancz Dóra
Cím:Flagellin increases death receptor-mediated cell death in a RIP1-dependent manner / Hancz Dora, Szabo Aniko, Molnar Tamás, Varga Zsofia, Hancz Aniko, Gregus Andrea, Hueber Anne-Odile, Rajnavolgyi Eva, Koncz Gabor
Dátum:2018
ISSN:0165-2478
Megjegyzések:Efficient adjuvants have the potential to trigger both innate and adaptive immune responses simultaneously. Flagellin is a unique pathogen-derived protein, which is recognized by pattern recognition receptors (PRRs) as well as by B-cell and T cell receptors thus providing an important link between innate and adaptive immunity. The aforementioned properties define flagellin as an optimal adjuvant. The induction of immunogenic cell death could be an additional expectation for adjuvants in the context of cancer immunotherapy due to their ability to activate dendritic cells (DC) to present tumor antigens through the engulfment of dying cells. The immunostimulatory potential of flagellin in the course of DC and lymphocyte activation is well documented, however the exact mechanism is not fully explored. Based on this limitation we sought to investigate the potential modulatory effects of flagellin on various cell death processes knowing that it plays detrimental roles in regulating the final outcome of various types of immune responses. Here we provide evidence that the pre-treatment of Jurkat T-cells with recombinant flagellin is able to increase the degree of cell death provoked by FasL or TNF-?, and concomitantly increases the cytotoxic potential of phytohemagglutinin activated T-lymphocytes in a TLR5 dependent way. In contrast to these flagellin-mediated effects on the death receptor-induced signaling events, the mitochondrial apoptotic pathway remained unaffected. Furthermore, the cell culture supernatant of wild type Salmonella enteritidis bacteria, but not their flagellin deficient variant, was able to enhance the Fas-induced cell death process. To define the molecular mechanisms of flagellin-mediated elevated levels of cell death we were able to detect the upregulation of RIP1-dependent signaling events. These findings demonstrate that the cooperative actions of pattern recognition and different death receptors are able to initiate the cell death process with the mobilization of RIP-dependent cell death modalities. This finding highlights the capability of flagellin to act as a potential adjuvant which is relevant for tumor immunotherapy.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Adjuvant
Apoptosis
Necroptosis
PAMP
T cell
TLR
Megjelenés:Immunology Letters. - 193 (2018), p. 42-50. -
További szerzők:Szabó Anikó Molnár Tamás (1989-) (molekuláris biológus) Varga Zsófia (1992-) (molekuláris biológus) Hancz Anikó Gregus Andrea (1980-) (biológus) Hueber, Anne-Odile Rajnavölgyi Éva (1950-) (immunológus) Koncz Gábor (1970-) (biológus, immunológus)
Pályázati támogatás:OTKA-114423
OTKA
GINOP-2.3.2-15-2016-00050
GINOP
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Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM039523
Első szerző:Koncz Gábor (biológus, immunológus)
Cím:Vesicles Released by Activated T Cells Induce Both Fas-Mediated RIP-Dependent Apoptotic and Fas-Independent Nonapoptotic Cell Deaths / Koncz, G., Hancz, A., Chakrabandhu, K., Gogolak, P., Kerekes, K., Rajnavolgyi, E., Hueber, Anne-Odile
Dátum:2012
ISSN:0022-1767
Megjegyzések:Activated T cells secrete Fas ligand (FasL)-containing vesicles (secreted vesicles) that induce death of target cells. We provide evidence that secreted vesicles from culture supernatants (Csup) of various origins are able to generate both Fas-dependent apoptotic and Fas-independent, nonapoptotic cell death. In the absence of Fas, the nonapoptotic, Fas-independent pathway could still induce cell death. In contrast to RIP-independent classical Fas-induced cell death triggered by cross-linked or membrane-bound FasL, CSup-derived stimuli-induced apoptosis exhibited unique molecular and enzymatic characteristics. It could be partially inhibited by blocking cathepsin D enzyme activity and required the presence of RIP. Whereas stimulation with CSup, derived from both FasL-overexpressing Jurkat cells and PBMC, could induce cell death, the requirements for Fas-associated death domain protein and caspase-9 were different between the two systems. Our study highlights an important distinction between cell contact-mediated and secreted vesicle-generated activation-induced cell death and also demonstrates that the type of the secreted vesicles can also modify the cell death route. We propose that besides cell-to-cell interaction-mediated Fas triggering, stimuli induced by secreted vesicles can mediate important additional cell death signals regulating activation-induced cell death under physiological conditions.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Molekuláris Medicina
Megjelenés:Journal Of Immunology. - 189 : 6 (2012), p. 2815-2823. -
További szerzők:Hancz Anikó Chakrabandhu, Krittalak Gogolák Péter (1968-) (biológus, immunológus) Kerekes Krisztina Rajnavölgyi Éva (1950-) (immunológus) Hueber, Anne-Odile
Pályázati támogatás:TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
Jelátviteli kapcsolatok ős- és dendritikus sejt altípusokban
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Intézményi repozitóriumban (DEA) tárolt változat
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5.

001-es BibID:BIBFORM072832
035-os BibID:(Cikkazonosító)1765 (WOS)000423430000013 (Scopus)85041329100
Első szerző:Szabó Attila (molekuláris biológus, immunológus, filozófus)
Cím:Immunomodulatory capacity of the serotonin receptor 5-HT2B in a subset of human dendritic cells / Szabo Attila, Gogolak Peter, Koncz Gabor, Foldvari Zsofia, Pazmandi Kitti, Miltner Noemi, Poliska Szilard, Bacsi Attila, Djurovic Srdjan, Rajnavolgyi Eva
Dátum:2018
ISSN:2045-2322
Megjegyzések:Serotonin is a monoamine neurotransmitter that signals through a wide array of receptors (5-HT1-7) many of which are also involved in immune processes. Dendritic cells (DCs) are crucial players in immune defense by bridging innate and adaptive immune responses via their vast repertoire of pattern recognition receptors and antigen-presenting capability. Although serotonin is known to influence immunity at many levels, cell type-specific expression and function of its receptors remains poorly understood. Here we aimed to study 5-HT1-7 expression and function in CD1a- and CD1a+ human monocyte-derived DCs (moDCs). We found that the 5-HT2B receptor-subtype is solely expressed by the inflammatory CD1a+ moDC subset. Specific 5-HT2B activation potently inhibited TLR2, TLR3, and TLR7/8-induced proinflammatory cytokine and chemokine (TNF-?, IL-6, IL-8, IP-10, IL-12) but not type I interferon-? responses. 5-HT2B agonism also interfered with the polarization of CD1a+ moDC-primed CD4+ T cells towards inflammatory Th1 and Th17 effector lymphocytes. Here we report the subset-specific expression and immunomodulatory function of 5-HT2B in human moDCs. Our results expand the biological role of 5-HT2B which may act not only as a neurotransmitter receptor, but also as an important modulator of both innate and adaptive immune responses.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Scientific Reports. - 8 (2018), p. 1-12. -
További szerzők:Gogolák Péter (1968-) (biológus, immunológus) Koncz Gábor (1970-) (biológus, immunológus) Földvári Zsófia Pázmándi Kitti Linda (1984-) (molekuláris biológus, immunológus) Miltner Noémi (1990-) (molekuláris biológus) Póliska Szilárd (1978-) (biológus) Bácsi Attila (1967-) (immunológus) Djurovic, Srdjan Rajnavölgyi Éva (1950-) (immunológus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00050
GINOP
PEOPLE-2013-COFUND
FP7
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Intézményi repozitóriumban (DEA) tárolt változat
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6.

001-es BibID:BIBFORM063227
Első szerző:Szabó Attila (molekuláris biológus, immunológus, filozófus)
Cím:RIG-I inhibits the MAPK-dependent proliferation of BRAF mutant melanoma cells via MKP-1 / Attila Szabo, Tunde Fekete, Gabor Koncz, Brahma V. Kumar, Kitti Pazmandi, Zsofia Foldvari, Balazs Hegedus, Tamas Garay, Attila Bacsi, Eva Rajnavolgyi, Arpad Lanyi
Dátum:2016
ISSN:0898-6568
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
RIG-I
PRR
MAPK
Interferon
Melanoma
Proliferation
Megjelenés:Cellular Signalling 28 : 5 (2016), p. 335-347. -
További szerzők:Fekete Tünde (1984-) (immunológus, molekuláris biológus, mikrobiológus) Koncz Gábor (1970-) (biológus, immunológus) Kumar, Brahma V. Pázmándi Kitti Linda (1984-) (molekuláris biológus, immunológus) Földvári Zsófia Hegedűs Balázs Garay Tamás Bácsi Attila (1967-) (immunológus) Rajnavölgyi Éva (1950-) (immunológus) Lányi Árpád (1962-) (biológus, immunológus)
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Intézményi repozitóriumban (DEA) tárolt változat
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7.

001-es BibID:BIBFORM088858
035-os BibID:(cikkazonosító)8847038 (WoS)000591736500001 (Scopus)85096040529
Első szerző:Veréb Zoltán (immunológus, mikrobiológus, molekuláris biológus)
Cím:Vessel Wall-Derived Mesenchymal Stromal Cells Share Similar Differentiation Potential and Immunomodulatory Properties with Bone Marrow-Derived Stromal Cells / Veréb Zoltán, Mázló Anett, Szabó Attila, Póliska Szilárd, Kiss Attila, Litauszky Krisztina, Koncz Gábor, Boda Zoltán, Rajnavölgyi Éva, Bácsi Attila
Dátum:2020
ISSN:1687-966X 1687-9678
Megjegyzések:This study is aimed at investigating the phenotype, differentiation potential, immunomodulatory properties, and responsivenessof saphenous vein vessel wall-derived mesenchymal stromal cells (SV-MSCs) to various TLR ligands and proinflammatory cytokines, aswell as comparing their features to those of theirbone marrow-derived counterparts (BM-MSCs).Methods. SV-MSCs were isolated byenzymatic digestion of the saphenous vein vessel wall. Phenotype analysis was carried out byflow cytometry and microscopy, whereasadipogenic, chondrogenic, and osteogenic differentiation potentials were tested inin vitroassays. For comparative analysis, theexpression of different stemness, proliferation, and differentiation-related genes was determined by Affymetrix gene array. To comparethe immunomodulatory properties of SV-MSCs and BM-MSCs, mixed lymphocyte reaction was applied. To investigate theirresponses to various activating stimuli, MSCs weretreated with TLR ligands (LPS, PolyI:C) or proinflammatory cytokines (TNF?,IL-1?,IFN?), and the expression of various early innate immune response-related genes was assessed by qPCR, while secretion ofselected cytokines and chemokines was measured by ELISA.Results. The isolated SV-MSCs were able to differentiate into bone, fat,and cartilage cells/directionin vitro. SV-MSCs expressed the most important MSC markers (CD29, CD44, CD73, CD90, and CD105)and shared almost identical phenotypic characteristics with BM-MSCs. Their gene expression pattern and activation pathways wereclose to those of BM-MSCs. SV-MSCs showed better immunosuppressive activity inhibiting phytohemagglutinin-induced Tlymphocyte proliferationin vitrothan BM-MSCs. Cellular responses to treatments mimicking inflammatory conditions werecomparable in the bone marrow- and saphenous vein-derived MSCs. Namely, similar to BM-MSCs, SV-MSCs secreted increasedamount of IL-6 and IL-8 after 12- or 24-hour treatment with LPS, PolyI:C, TNF?,orIL-1?,comparedtountreatedcontrols.Interestingly, a different CXCL-10/IP-10 secretion pattern could be observed under inflammatory conditions in the two types ofMSCs.Conclusion. Based on our results, cells isolated from saphenous vein vessel wall fulfilled the ISCT's (International Society forCellular Therapy) criteria for multipotent mesenchymal stromal cells, and no significant differences in the phenotype, gene expressionpattern, and responsiveness to inflammatory stimuli could be observed between BM-MSCs and SV-MSCs, while the latter cells havemore potent immunosuppressive activityin vitro. Further functional assays have to be performed to reveal whether SV-MSCs couldbe useful for certain regenerative therapeutic applications or tissueengineering purposes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Stem Cells International. - 2020 (2020), p. 1-16. -
További szerzők:Türk-Mázló Anett (1989-) (molekuláris biológus) Szabó Attila (1981-) (molekuláris biológus, immunológus, filozófus) Póliska Szilárd (1978-) (biológus) Kiss Attila (1942-) (belgyógyász, haematológus) Litauszky Krisztina (1967-) (orvos) Koncz Gábor (1970-) (biológus, immunológus) Boda Zoltán (1947-) (belgyógyász, haematologus, klinikai onkológus) Rajnavölgyi Éva (1950-) (immunológus) Bácsi Attila (1967-) (immunológus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00050
GINOP
OTKA-114423
OTKA
NKFIH K 125337
Egyéb
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Intézményi repozitóriumban (DEA) tárolt változat
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