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1.

001-es BibID:BIBFORM071907
035-os BibID:(WoS)000423384000001 (Scopus)85041107428
Első szerző:Agod Zsófia
Cím:Signaling Lymphocyte Activation Molecule Family 5 Enhances Autophagy and Fine-Tunes Cytokine Response in Monocyte-Derived Dendritic Cells via Stabilization of Interferon Regulatory Factor 8 / Zsofia Agod, Kitti Pazmandi, Dora Bencze, Gyorgy Vereb, Tamas Biro, Attila Szabo, Eva Rajnavolgyi, Attila Bacsi, Pablo Engel, Arpad Lanyi
Dátum:2018
ISSN:1664-3224
Megjegyzések:Signaling lymphocyte activation molecule family (SLAMF) receptors are essential regulators of innate and adaptive immune responses. The function of SLAMF5/CD84, a family member with almost ubiquitous expression within the hematopoietic lineage is poorly defined. In this paper we provide evidence that in human monocyte-derived dendritic cells (moDCs) SLAMF5 increases autophagy, a degradative pathway, which is highly active in dendritic cells (DCs) and plays a critical role in orchestration of the immune response. While investigating the underlying mechanism, we found that SLAMF5 inhibited proteolytic degradation of interferon regulatory factor 8 (IRF8) a master regulator of the autophagy process by a mechanism dependent on the E3 ubiquitin ligase tripartite motif-containing protein 21 (TRIM21). Furthermore, we demonstrate that SLAMF5 influences the ratio of CD1a+ cells in differentiating DCs and partakes in the regulation of IL?1?, IL?23 and IL?12 production in LPS/IFN??activated moDCs in a manner that is consistent with its effect on IRF8 stability. In summary, our experiments identified SLAMF5 as a novel cell surface receptor modulator of autophagy and revealed an unexpected link between the SLAMF and IRF8 signaling pathways, both implicated in multiple human pathologies.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
SLAMF5
Autophagy
Dendritic Cells
IRF8
TRIM21
IL?12p70
LPS/IFN?
Megjelenés:Frontiers in Immunology. - 9 (2018), p. 1-16. -
További szerzők:Pázmándi Kitti Linda (1984-) (molekuláris biológus, immunológus) Bencze Dóra (1992-) Vereb György (1965-) (biofizikus, orvos) Bíró Tamás (1968-) (élettanász) Szabó Attila (1981-) (molekuláris biológus, immunológus, filozófus) Rajnavölgyi Éva (1950-) (immunológus) Bácsi Attila (1967-) (immunológus) Engel, Pablo Lányi Árpád (1962-) (biológus, immunológus)
Pályázati támogatás:NKFIH K 81676
Egyéb
NKFIH K 109444
Egyéb
Romanian Ministry of Education, Executive Agency For Higher Education, Research, Development and Innovation Funding, PNCDI II, project no. 119/2014
Egyéb
GINOP-2.3.2-15-2016-00050
GINOP
COST Action BM1404 Mye-EUNITER
Egyéb
János Bolyai Research Scholarship from the Hungarian Academy of Sciences
Egyéb
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2.

001-es BibID:BIBFORM131144
035-os BibID:(wos)001528019400001 (Scopus)105011040443
Első szerző:Ahmad, Hala
Cím:Retinoic acid differently modulates NOD1/NOD2-mediated inflammatory responses in human macrophage subsets / Ahmad Hala, Alatshan Ahmad, Bíró Eduárd, Benkő Szilvia
Dátum:2025
ISSN:1664-3224
Megjegyzések:Macrophages are indispensable in homeostasis and innate immune responses in multiple tissues, while their polarization and functional characteristics are determined by the activating stimuli and their tissue microenvironment. The vitamin A derivative retinoic acid shows inhomogeneous distribution among the tissues and has an important modulatory role in inflammatory responses. However, its effects on the cytokine secretion induced by the cytosolic pattern-recognition receptors NOD1 and NOD2 are unclear. In our study, we used human monocyte-derived macrophages differentiated in the presence of GM-CSF or M-CSF to generate inflammation inducing (GM-M?) or inflammation resolving (M-M?) cells, respectively. We activated the cells with either a NOD1- or NOD2 specific agonist and, using ELISA, we determined the pattern and dynamics of cytokines secreted by the macrophage subpopulations. Furthermore, we studied the effect of all-trans retinoic acid (ATRA) pre-treatment on the NOD1- and NOD2-induced cytokine release. Our comparative analysis shows subpopulation-characteristic pattern of cytokine secretion, as GM-M? produce significantly higher pro-inflammatory IL-6, IL-8, TNF-? and IL-1?, while M-M? secret higher anti-inflammatory IL-10. However, IL-18 and IFN? secretion was comparable between the M? subpopulations. We also show for the first time that ATRA has marked impact on cytokine secretion triggered by NOD1 and NOD2. Importantly however, the ATRA-induced changes of cytokine secretion follow opposite tendency in two M? subpopulations. In conclusion, these results show that NOD1/NOD2-induced cytokine secretion by macrophage subsets is highly context-dependent and our results highlight the importance of the retinoic acid content of the local tissue environment in shaping macrophage function in health and disease.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
retinoic acid
NOD1
NOD2
NOD-like receptor
vitamin A
inflammation
macrophage
cytokine
Megjelenés:Frontiers in Immunology. - 16 (2025), p. 1-11. -
További szerzők:Alatshan, Ahmad (1984-) (immunológus) Bíró Eduárd (1998-) (molekuláris biológus) Benkő Szilvia (1973-) (molekuláris biológus)
Pályázati támogatás:K131844
OTKA
K147109
OTKA
Richter Talentum Foundation
Egyéb
Stipendium Hungaricum Scholarship
Egyéb
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3.

001-es BibID:BIBFORM098738
035-os BibID:(WoS)000627757800001 (Scopus)85102440838
Első szerző:Alatshan, Ahmad (immunológus)
Cím:Nuclear Receptors as Multiple Regulators of NLRP3 Inflammasome Function / Alatshan Ahmad, Benkő Szilvia
Dátum:2021
ISSN:1664-3224
Megjegyzések:Nuclear receptors are important bridges between lipid signaling molecules and transcription responses. Beside their role in several developmental and physiological processes, many of these receptors have been shown to regulate and determine the fate of immune cells, and the outcome of immune responses under physiological and pathological conditions. While NLRP3 inflammasome is assumed as key regulator for innate and adaptive immune responses, and has been associated with various pathological events, the precise impact of the nuclear receptors on the function of inflammasome is hardly investigated. A wide variety of factors and conditions have been identified as modulators of NLRP3 inflammasome activation, and at the same time, many of the nuclear receptors are known to regulate, and interact with these factors, including cellular metabolism and various signaling pathways. Nuclear receptors are in the focus of many researches, as these receptors are easy to manipulate by lipid soluble molecules. Importantly, nuclear receptors mediate regulatory mechanisms at multiple levels: not only at transcription level, but also in the cytosol via non-genomic effects. Their importance is also reflected by the numerous approved drugs that have been developed in the past decade to specifically target nuclear receptors subtypes. Researches aiming to delineate mechanisms that regulate NLRP3 inflammasome activation draw a wide range of attention due to their unquestionable importance in infectious and sterile inflammatory conditions. In this review, we provide an overview of current reports and knowledge about NLRP3 inflammasome regulation from the perspective of nuclear receptors, in order to bring new insight to the potentially therapeutic aspect in targeting NLRP3 inflammasome and NLRP3 inflammasome-associated diseases.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
inflammasome
NLRP3
IL-1
signaling
PPAR
LXR
PXR
metabolism
Megjelenés:Frontiers in Immunology. - 12 (2021), p. 630569. -
További szerzők:Benkő Szilvia (1973-) (molekuláris biológus)
Pályázati támogatás:K131844
OTKA
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4.

001-es BibID:BIBFORM068268
035-os BibID:(WoS)000399425000003 (Scopus)85018375753
Első szerző:Bene Krisztián (Biológus)
Cím:Gut Microbiota Species Can Provoke both Inflammatory and Tolerogenic Immune Responses in Human Dendritic Cells Mediated by Retinoic Acid Receptor Alpha Ligation / Krisztian Bene, Zsofia Varga, Viktor O. Petrov, Nadiya Boyko, Eva Rajnavolgyi
Dátum:2017
Megjegyzések:Dendritic cells are considered as the main coordinators of both mucosal and systemic immune responses, thus playing a determining role in shaping the outcome of effector cell responses. However, it is still uncovered how primary human monocyte-derived DC (moDC) populations drive the polarization of helper T (Th) cells in the presence of commensal bacteria harboring unique immunomodulatory properties. Furthermore,the individual members of the gut microbiota have the potential to modulate the outcomeof immune responses and shape the immunogenicity of differentiating moDCsvia the activation of retinoic acid receptor alpha (RAR?). Here, we report that moDCs are able to mediate robust Th1 and Th17 responses upon stimulation by Escherichiacoli Schaedler or Morganella morganii, while the probiotic Bacillus subtilis strain limits this effect. Moreover, physiological concentrations of all-trans retinoic acid (ATRA) are able to re-program the differentiation of moDCs resulting in altered gene expression profiles of the master transcription factors RAR? and interferon regulatory factor 4, andconcomitantly regulate the cell surface expression levels of CD1 proteins and also the mucosa-associated CD103 integrin to different directions. It was also demonstrated that the ATRA-conditioned moDCs exhibited enhanced pro-inflammatory cytokine secretion while reduced their co-stimulatory and antigen-presenting capacity thus reducing Th1 and presenting undetectable Th17 type responses against the tested microbiota strains.Importantly, these regulatory circuits could be prevented by the selective inhibition of RAR? functionality. These results altogether demonstrate that selected commensal bacterialstrains are able to drive strong effector immune responses by moDCs, while in the presence of ATRA, they support the development of both tolerogenic and inflammatory moDC in a RAR?-dependent manner.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
immunológia
mikrobiológia
dendritikus sejt
mikrobióta
A-vitamin
retinsav
T sejt
Megjelenés:Frontiers in Immunology. - 8 : 427 (2017), p. 1-17. -
További szerzők:Varga Zsófia (1992-) (molekuláris biológus) Petrov, Viktor O. Boyko, Nadiya V. Rajnavölgyi Éva (1950-) (immunológus)
Pályázati támogatás:TAMOP 4.2.4.A/2-11-1- 2012-0001
TÁMOP
TAMOP 4.2.2.A-11/1/KONV-2012-0023
TÁMOP
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5.

001-es BibID:BIBFORM052625
Első szerző:Budai Marietta Margit (molekuláris biológus)
Cím:Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages / Marietta M. Budai, Aliz Varga, Sándor Milesz, József Tőzsér, Szilvia Benkő
Dátum:2013
ISSN:0161-5890
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Molecular Immunology 56 : 4 (2013), p. 471-479. -
További szerzők:Varga Alíz (1983-) (immunológus) Milesz Sándor Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Benkő Szilvia (1973-) (molekuláris biológus)
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6.

001-es BibID:BIBFORM136569
Első szerző:Caballero-Sánchez, Noemí (PhD hallgató)
Cím:BACH1 orchestrates macrophage state transitions to coordinate regenerative inflammation / Noemí Caballero-Sánchez, Petros Tzerpos, Krisztian Bene, Laszlo Halasz, Dóra Bojcsuk, Gergely Nagy, Maysaa A. Ali, Timea Cseh, Szilard Poliska, Matthew J. Borok, Jordan Scherer, Frederic Relaix, Enrique Saez, Zsolt Czimmerer, Andreas Patsalos, Laszlo Nagy
Dátum:2026
ISSN:0022-1767 1550-6606
Megjegyzések:Efficient tissue regeneration requires the precise coordination of inflammatory and regenerative programs, principally mediated by monocyte-derived macrophages. However, the transcriptional wiring and epigenomic processes behind complex macrophage subtype specification and transition between the different states are not known. Here we have identified the transcriptional repressor BACH1 as a critical, cell-intrinsic regulator of monocyte-derived macrophage specification during skeletal muscle regeneration. Using a myeloid-specific BACH1 knockout mouse model, we demonstrate that BACH1 deficiency disrupts the temporal coordination of monocyte-to-macrophage differentiation, leading to aberrant macrophage subsets with concurrent opposing pro-and anti-inflammatory features. Single-cell RNA-sequencing profiling reveals that BACH1 controls a core transcriptional network, including Nfkb1, Cebpb, and interferon signaling, governing inflammatory resolution and functional macrophage specialization. Mechanistically, BACH1 loss accelerates macrophage differentiation but also affects its core cellular identity, resulting in sustained, rather than declining inflammatory programs including upregulation of Il1b and thus, defective tissue remodeling. These immune alterations compromise the paracrine landscape during regenerative inflammation and impair muscle stem cell differentiation. Our findings establish BACH1 as a molecular tuner or controller that integrates early innate immune signaling with regenerative output, positioning it as a central node linking transcriptional control, immune fate decisions, and tissue repair.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
BACH1
transcription factor
inflammation
regenerative inflammation
muscle repair
Megjelenés:Journal Of Immunology. - "Accepted by Publisher" (2026). -
További szerzők:Tzerpos, Petros (1982-) (molekuláris biológus) Bene Krisztián (1986-) (Biológus) Halász László (1989-) (molekuláris biológus) Bojcsuk Dóra (1990-) (klinikai laboratóriumi kutató) Nagy Gergely (1986-) (molekuláris biológus) Ali, Maysaa Adil (1983-) (biotechnológus) Silye-Cseh Timea (1985-) (Biológus) Póliska Szilárd (1978-) (biológus) Borok, Matthew J. Scherer, Jordan Relaix, Frederic Saez, Enrique Czimmerer Zsolt (1981-) (molekuláris biológus) Patsalos, Andreas Nagy László (1966-) (molekuláris sejtbiológus, biokémikus)
Pályázati támogatás:Marie Skodowska-Curie
Egyéb
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7.

001-es BibID:BIBFORM014049
Első szerző:Csillag Anikó (immunológus, biológus, angol-magyar szakfordító)
Cím:Pollen-Induced Oxidative Stress Influences Both Innate and Adaptive Immune Responses via Altering Dendritic Cell Functions / Csillag, A., Boldogh, I., Pazmandi, K., Magyarics, Z., Gogolak, P., Sur, S., Rajnavolgyi, E., Bacsi, A.
Dátum:2010
ISSN:0022-1767
Megjegyzések:It has been demonstrated that pollen grains contain NAD(P)H oxidases that induce oxidative stress in the airways, and this oxidative insult is critical for the development of allergic inflammation in sensitized mice. On the basis of this observation, we have examined whether pollen grain exposure triggers oxidative stress in dendritic cells (DCs), altering their functions. To test this hypothesis, human monocyte-derived DCs were treated with ragweed pollen grains. Our findings show that exposure to pollen grains induces an increase in the intracellular levels of reactive oxygen species in DCs. Our data also indicate that besides the NAD(P)H oxidases, other component(s) of pollen grains contributes to this phenomenon. Elevated levels of intracellular reactive oxygen species triggered the production of IL-8 as well as proinflammatory cytokines, such as TNF-alpha and IL-6. Treatment with pollen grains initiated the maturation of DCs, strongly upregulated the membrane expression of CD80, CD86, CD83, and HLA-DR, and caused only a slight increase in the expression of CD40. The pollen-treated DCs induced the development of naive T lymphocytes toward effector T cells with a mixed profile of cytokine production. Antioxidant inhibited both the phenotypic and functional changes of DCs, underlining the importance of oxidative stress in these processes. Collectively, these data show that pollen exposure-induced oxidative stress may contribute to local innate immunity and participate in the initiation of adaptive immune responses to pollen Ags.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Allergic Airway Inflammation
Exhaust Particle Chemicals
Tight Junctions
NADPH Oxidase
T-Cells
Maturation
Phytoprostanes
Proteins
Extracts
Gamma
Megjelenés:Journal of Immunology. - 184 : 5 (2010), p. 2377-2385. -
További szerzők:Boldogh István Pázmándi Kitti Linda (1984-) (molekuláris biológus, immunológus) Magyarics Zoltán (1982-) (immunológus) Gogolák Péter (1968-) (biológus, immunológus) Sur, Sanjiv Rajnavölgyi Éva (1950-) (immunológus) Bácsi Attila (1967-) (immunológus)
Pályázati támogatás:NK 72937
OTKA
GVOP-3.1.1.-2004-05-0393/3.0
Egyéb
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8.

001-es BibID:BIBFORM111612
035-os BibID:(scopus)85159842579 (wos)000989034400001
Első szerző:Domokos Apolka
Cím:The transcriptional control of the VEGFA-VEGFR1 (FLT1) axis in alternatively polarized murine and human macrophages / Domokos Apolka, Varga Zsofia, Jambrovics Karoly, Caballero-Sánchez Noemí, Szabo Eniko, Nagy Gergely, Scholtz Beata, Halasz Laszlo, Varadi Eszter, Bene Krisztian P., Mazlo Anett, Bacsi Attila, Jeney Viktoria, Szebeni Gabor J., Nagy Laszlo, Czimmerer Zsolt
Dátum:2023
ISSN:1664-3224
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Frontiers in Immunology. - 14 (2023), p.1-20. -
További szerzők:Varga Zsófia (1992-) (molekuláris biológus) Jambrovics Károly (1988-) (biológus, gyógyszer-biotechnológus) Caballero-Sánchez, Noemí (1995-) (PhD hallgató) Szabó Enikő Nagy Gergely (1986-) (molekuláris biológus) Scholtz Beáta (1967-) (biokémikus, molekuláris biológus) Halász László (1989-) (molekuláris biológus) Váradi Eszter Bene Krisztián (1986-) (Biológus) Türk-Mázló Anett (1989-) (molekuláris biológus) Bácsi Attila (1967-) (immunológus) Jeney Viktória (1971-) (vegyész, kémia tanár) Szebeni Gábor János (Szeged) Nagy László (1966-) (molekuláris sejtbiológus, biokémikus) Czimmerer Zsolt (1981-) (molekuláris biológus)
Pályázati támogatás:FK132185
OTKA
ÚNKP-22-5-SZTE-549
Egyéb
2020?1.1.6-JÖVŐ-2021-00003
Egyéb
ÚNKP-22-5-SZTE-535
Egyéb
142877 FK22
Egyéb
PD142930
OTKA
PD135102
OTKA
K131535
OTKA
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9.

001-es BibID:BIBFORM085388
035-os BibID:(WoS)000524776500001 (Scopus)85082380165
Első szerző:Erdei Judit Zsuzsa (vegyész)
Cím:The Role of Hemoglobin Oxidation Products in Triggering Inflammatory Response Upon Intraventricular Hemorrhage in Premature Infants / Erdei Judit, Tóth Andrea, Nagy Andrea, Nyakundi Benard Bogonko, Fejes Zsolt, Nagy Béla Jr., Novák László, Bognár László, Balogh Enikö, Paragh György, Kappelmayer János, Bácsi Attila, Jeney Viktória
Dátum:2020
ISSN:1664-3224
Megjegyzések:Intraventricular hemorrhage (IVH) is a frequent complication of prematurity that is associated with high neonatal mortality and morbidity. IVH is accompanied by red blood cell (RBC) lysis, hemoglobin (Hb) oxidation, and sterile inflammation. Here we investigated whether extracellular Hb, metHb, ferrylHb, and heme contribute to the inflammatory response after IVH. We collected cerebrospinal fluid (CSF) (n = 20) from premature infants with grade III IVH at different time points after the onset of IVH. Levels of Hb, metHb, total heme, and free heme were the highest in CSF samples obtained between days 0 and 20 after the onset of IVH and were mostly non-detectable in CSF collected between days 41 and 60 of post-IVH. Besides Hb monomers, we detected cross-linked Hb dimers and tetramers in post-IVH CSF samples obtained in days 0-20 and 21-40, but only Hb tetramers were present in CSF samples obtained after 41-60 days. Vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8) levels were higher in CSF samples obtained between days 0 and 20 than in CSF collected between days 41 and 60 of post-IVH. Concentrations of VCAM-1, intercellular adhesion molecule-1 (ICAM-1), and IL-8 strongly correlated with total heme levels in CSF. Applying the identified heme sources on human brain microvascular endothelial cells revealed that Hb oxidation products and free heme contribute to the inflammatory response. We concluded that RBC lysis, Hb oxidation, and heme release are important components of the inflammatory response in IVH. Pharmacological interventions targeting cell-free Hb, Hb oxidation products, and free heme could have potential to limit the neuroinflammatory response following IVH.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Frontiers in Immunology. - 11 (2020), p. 228. -
További szerzők:Tóth Andrea (1992-) (molekuláris biológus) Nagy Andrea (1958-) (csecsemő és gyermekgyógyász, neonatológus) Nyakundi, Benard Bogonko (1983-) (biokémikus) Fejes Zsolt (1988-) (molekuláris biológus) Nagy Béla Jr. (1980-) (labordiagnosztikai szakorvos) Novák László (1964-) (idegsebész) Bognár László (1958-) (idegsebész, gyermekidegsebész) Balogh Enikő (1987-) (molekuláris biológus) Paragh György (1953-) (belgyógyász) Kappelmayer János (1960-) (laboratóriumi szakorvos) Bácsi Attila (1967-) (immunológus) Jeney Viktória (1971-) (vegyész, kémia tanár)
Pályázati támogatás:GINOP-2.3.2-15-2016-00005
GINOP
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10.

001-es BibID:BIBFORM088738
035-os BibID:(WoS)000576009300001 (Scopus)85091480359
Első szerző:Fekete Tünde (immunológus, molekuláris biológus, mikrobiológus)
Cím:Regulation of RLR-Mediated Antiviral Responses of Human Dendritic Cells by mTOR / Fekete Tünde, Ágics Beatrix, Bencze Dóra, Bene Krisztián, Szántó Antónia, Tarr Tünde, Veréb Zoltán, Bácsi Attila, Pázmándi Kitti
Dátum:2020
ISSN:1664-3224
Megjegyzések:To detect replicating viruses, dendritic cells (DCs) utilize cytoplasmic retinoic acid inducible gene-(RIG) I-like receptors (RLRs), which play an essential role in the subsequent activation of antiviral immune responses. In this study, we aimed to explore the role of the mammalian target of rapamycin (mTOR) in the regulation of RLR-triggered effector functions of human monocyte-derived DCs (moDCs) and plasmacytoid DCs (pDCs). Our results show that RLR stimulation increased the phosphorylation of the mTOR complex (mTORC) 1 and mTORC2 downstream targets p70S6 kinase and Akt, respectively, and this process was prevented by the mTORC1 inhibitor rapamycin as well as the dual mTORC1/C2 kinase inhibitor AZD8055 in both DC subtypes. Furthermore, inhibition of mTOR in moDCs impaired the RLR stimulation-triggered glycolytic switch, which was reflected by the inhibition of lactate production and downregulation of key glycolytic genes. Blockade of mTOR diminished the ability of RLR-stimulated moDCs and pDCs to secret type I interferons (IFNs) and pro-inflammatory cytokines, while it did not affect the phenotype of DCs. We also found that mTOR blockade decreased the phosphorylation of Tank-binding kinase 1 (TBK1), which mediates RLR-driven cytokine production. In addition, rapamycin abrogated the ability of both DC subtypes to promote the proliferation and differentiation of IFN-y and Granzyme B producing CD8 + T cells. Interestingly, AZD8055 was much weaker in its ability to decrease the T cell proliferation capacity of DCs and was unable to inhibit the DC-triggered production of IFN-y and Granyzme B by CD8 + T cells. Here we demonstrated for the first time that mTOR positively regulates the RLR-mediated antiviral activity of human DCs. Further, we show that only selective inhibition of mTORC1 but not dual mTORC1/C2 blockade suppresses effectively the T cell stimulatory capacity of DCs that should be considered in the development of new generation mTOR inhibitors and in the improvement of DC-based vaccines.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
RLR signaling
T cell stimulation
antiviral response
dendritic cell
mTOR
Megjelenés:Frontiers in Immunology. - 11 (2020), p. 1-20. -
További szerzők:Ágics Beatrix (1995-) (molekuláris biológus) Bencze Dóra (1992-) Bene Krisztián (1986-) (Biológus) Szántó Antónia (1977-) (belgyógyász, allergológus és klinikai immunológus) Tarr Tünde (1976-) (belgyógyász, allergológus és klinikai immunológus) Veréb Zoltán (1980-) (immunológus, mikrobiológus, molekuláris biológus) Bácsi Attila (1967-) (immunológus) Pázmándi Kitti Linda (1984-) (molekuláris biológus, immunológus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00050
GINOP
FK 128294
NKFIH
UNKP 19-4
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

11.

001-es BibID:BIBFORM076291
035-os BibID:(WoS)000454093300001 (Scopus)85059796010
Első szerző:Fekete Tünde (immunológus, molekuláris biológus, mikrobiológus)
Cím:Human Plasmacytoid and Monocyte-Derived Dendritic Cells Display Distinct Metabolic Profile Upon RIG-I Activation / Tünde Fekete, Máté I. Sütő, Dóra Bencze, Anett Mázló, Attila Szabo, Tamas Biro, Attila Bacsi, Kitti Pázmándi
Dátum:2018
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Frontiers in Immunology. - 9 (2018), p. 1-32. -
További szerzők:Sütő Máté István (1991-) (molekuláris biológus) Bencze Dóra (1992-) Türk-Mázló Anett (1989-) (molekuláris biológus) Szabó Attila (1981-) (molekuláris biológus, immunológus, filozófus) Bíró Tamás (1968-) (élettanász) Bácsi Attila (1967-) (immunológus) Pázmándi Kitti Linda (1984-) (molekuláris biológus, immunológus)
Pályázati támogatás:NKFIH PD 115776
NKFIH
NKFIH PD 16 120887
NKFIH
GINOP-2.3.2-15-2016-00050
GINOP
EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:

12.

001-es BibID:BIBFORM075433
035-os BibID:(WoS)000446446200002 (Scopus)85055075977
Első szerző:Fekete Tünde (immunológus, molekuláris biológus, mikrobiológus)
Cím:Regulatory NLRs Control the RLR-Mediated Type I Interferon and Inflammatory Responses in Human Dendritic Cells / Tünde Fekete, Dora Bencze, Attila Szabo, Eszter Csoma, Tamas Biro, Attila Bacsi, Kitti Pazmandi
Dátum:2018
ISSN:1664-3224
Megjegyzések:Unique members of the nucleotide-binding domain leucine-rich repeat (NLR) family have been found to regulate intracellular signaling pathways initiated by other families of pattern recognition receptors (PRR) such as Toll-like receptors (TLRs) and retinoic-acid inducible gene I (RIG-I)-like receptors (RLRs). Plasmacytoid dendritic cells (pDCs), the most powerful type I interferon (IFN) producing cells, preferentially employ endosomal TLRs to elicit antiviral IFN responses. By contrast, conventional DCs (cDCs) predominantly use cytosolic RLRs, which are constitutively expressed in them, to sense foreign nucleic acids. Previously we have reported that, though RIG-I is absent from resting pDCs, it is inducible upon TLR stimulation. In the recent study we investigated the regulatory ability of NLRs, namely NLRC5 and NLRX1 directly associated with the RLR-mediated signaling pathway in DC subtypes showing different RLR expression, particularly in pDCs, and monocyte-derived DCs (moDCs). Here we demonstrate that similarly to RLRs, NLRC5 is also inducible upon TLR9 stimulation, whereas NLRX1 is constitutively expressed in pDCs. Inhibition of NLRC5 and NLRX1 expression in pDCs augmented the RLR-stimulated expression of type I IFNs but did not affect the production of the pro-inflammatory cytokines TNF, IL-6, and the chemokine IL-8. Further we show that immature moDCs constantly express RLRs, NLRX1 and NLRC5 that are gradually upregulated during their differentiation. Similarly to pDCs, NLRX1 suppression increased the RLR-induced production of type I IFNs in moDCs. Interestingly, RLR stimulation of NLRX1-silenced moDCs leads to a significant increase in pro-inflammatory cytokine production and I?Bα degradation, suggesting increased NF-?B activity. On the contrary, NLRC5 does not seem to have any effect on the RLR-mediated cytokine responses in moDCs. In summary, our results indicate that NLRX1 negatively regulates the RLR-mediated type I IFN production both in pDCs and moDCs. Further we show that NLRX1 inhibits pro-inflammatory cytokine secretion in moDCs but not in pDCs following RLR stimulation. Interestingly, NLRC5 suppresses the RLR-induced type I IFN secretion in pDCs but does not appear to have any regulatory function on the RLR pathway in moDCs. Collectively, our work demonstrates that RLR-mediated innate immune responses are primarily regulated by NLRX1 and partly controlled by NLRC5 in human DCs.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Frontiers in Immunology. - 9 (2018), p. 1-19. -
További szerzők:Bencze Dóra (1992-) Szabó Attila (1981-) (molekuláris biológus, immunológus, filozófus) Csoma Eszter (1978-) (molekuláris biológus, mikrobiológus) Bíró Tamás (1968-) (élettanász) Bácsi Attila (1967-) (immunológus) Pázmándi Kitti Linda (1984-) (molekuláris biológus, immunológus)
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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