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001-es BibID:	BIBFORM088738
035-os BibID:	(cikkazonosító)572960 (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-) 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
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001-es BibID:	BIBFORM093501
035-os BibID:	(cikkazonosító)639308 (WoS)000645544400001 (Scopus)85105218104
Első szerző:	Papp Gábor (belgyógyász)
Cím:	Regular Exercise May Restore Certain Age-Related Alterations of Adaptive Immunity and Rebalance Immune Regulation / Gábor Papp, Krisztina Szabó, Ilona Jámbor, Marianna Mile, Alexandra Réka Berki, Attila Csaba Arany, Gabriella Makra, Peter Szodoray, Zoltán Csiki, László Balogh
Dátum:	2021
ISSN:	1664-3224
Megjegyzések:	Age-related changes of the immune system lead to an increased morbidity and mortality due to enhanced vulnerability to infectious diseases and malignancies. Recent studies revealed the important effects of physical activity on immune functions, which may largely depend on the type of exercise, its intensity and duration. However, limited information is available regarding the immunological effects of sport activities in older ages. The aim of our study was to examine the changes in a wide spectrum of lymphocyte subtypes after regular workout among healthy elderly individuals. We enrolled 29 elderly women with sedentary lifestyle (mean age: 67.03 ? 3.74 years) to take part in a 6-week long functional conditioning gymnastic exercise program. The percentages of peripheral natural killer (NK), NKT cells, T and B lymphocyte subtypes (early-/late-activated T, naïve and memory T, cytotoxic T (Tc), T-helper (Th)1, Th2, Th17, T regulatory type 1 (Tr1), CD4+CD127lo/-CD25bright Treg, as well as naïve and memory B cells) were determined by flow cytometry. Evaluation of the changes in functional capability of Treg cells was based on in vitro functional assays. At the end of exercise program, in parallel with improvements in body composition and physical performance, significant changes in naïve and memory lymphocyte ratios were observed. Importantly, levels of naïve Tc cells elevated, ratios of effector memory Tc cells decreased and distribution of memory B cells rearranged as well. Additionally, proportions of late-activated HLA-DR+ T cells increased, while percentages of anti-inflammatory interleukin (IL)-10 producing Tr1 cells, as well as immunosuppressive CD4+CD127lo/-CD25bright Treg cells decreased following the exercise workout. Changes observed after the regular exercise program indicate an improvement in the age-related redistribution of certain naïve and memory cell proportions and a retuned immune regulation in older ages.
Tárgyszavak:	Orvostudományok Sporttudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk aging immunosenescence physical activity exercise immune regulation
Megjelenés:	Frontiers in Immunology. - 12 (2021), p. 1-13. -
További szerzők:	Szabó Krisztina (1987-) (Molekuláris biológus) Jámbor Ilona (1985-) (orvosi biotechológus) Mile Marianna (1977-) (gyógytornász) Berki Alexandra Réka (1994-) (orvos) Arany Attila Csaba (1998-) (gyógytornász) Makra Gabriella Szodoray Péter (1973-) (belgyógyász, orvos) Csiki Zoltán (1962-) (belgyógyász, allergológus, klinikai immunológus, reumatológus) Balogh László (1976-) (sporttudomány)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00062 GINOP EFOP-3.6.1-16-2016-00022 EFOP ÚNKP-20-5 New National Excellence Program Egyéb János Bolyai Research Scholarship Egyéb
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001-es BibID:	BIBFORM092150
035-os BibID:	(cikkazonosító)639975 (WoS)000635978100001 (Scopus)85103554422
Első szerző:	Szabó Krisztina (Molekuláris biológus)
Cím:	The imbalance of circulating follicular T helper cell subsets in primary Sjögren's syndrome associates with serological alterations and abnormal B-cell distribution / Krisztina Szabó, Ilona Jámbor, Antónia Szántó, Ildikó Fanny Horváth, Tünde Tarr, Britt Nakken, Péter Szodoray, Gábor Papp
Dátum:	2021
ISSN:	1664-3224
Megjegyzések:	Since B-cell hyperactivity and pathologic antibody response are key features in the immunopathogenesis of primary Sjögren's syndrome (pSS), the role of follicular T helper (TFH) cells as efficient helpers in the survival and differentiation of B cells has been emerged. Our aim was to investigate whether a change in the balance of circulating (c)TFH subsets and follicular regulatory T (TFR) cells could affect the distribution of B cells in pSS. Peripheral blood of 38 pSS patients and 27 healthy controls was assessed for the frequencies of cTFH cell subsets, TFR cells and certain B cell subpopulations by multicolor flow cytometry. Serological parameters, including anti-SSA, anti-SSB autoantibodies, immunoglobulin and immune complex titers were determined as part of the routine diagnostic evaluation. Patients with pSS showed a significant increase in activated cTFH cell proportions, which was associated with serological results. Frequencies of cTFH subsets were unchanged in pSS patients compared to healthy controls. The percentages and number of cTFR cells exhibited a significant increase in autoantibody positive patients compared to patients with seronegative pSS. The proportions of transitional and naïve B cells were significantly increased, whereas subsets of memory B cells were significantly decreased and correlated with autoantibody production. Functional analysis revealed that the simultaneous blockade of cTFH and B cell interaction with anti-IL-21 and anti-CD40 antibodies decreased the production of IgM and IgG. Imbalance in TFH subsets and TFR cells indicates an ongoing over-activated humoral immune response, which contributes to the characteristic serological manifestations and the pathogenesis of pSS.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk follicular T helper cell follicular regulatory T cell Chemokine receptors B cells primary Sjögren's syndrome
Megjelenés:	Frontiers in Immunology. - 12 (2021), p. 1-13. -
További szerzők:	Jámbor Ilona (1985-) (orvosi biotechológus) Szántó Antónia (1977-) (belgyógyász, allergológus és klinikai immunológus) Horváth Ildikó Fanny (1980-) (belgyógyász, allergológus, klinikai immunológus) Tarr Tünde (1976-) (belgyógyász, allergológus és klinikai immunológus) Nakken, Britt Szodoray Péter (1973-) (belgyógyász, orvos) Papp Gábor (1984-) (belgyógyász)
Pályázati támogatás:	121327 PD_16 124177 OTKA
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