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001-es BibID:BIBFORM106381
035-os BibID:(PMID)36502939 (WoS)000984536200001 (Scopus)85149686723
Első szerző:Alimohammadi, Shahrzad (Gyógyszerész)
Cím:TRPV4 activation increases the expression of CD207 (Langerin) of monocyte-derived Langerhans cells, without affecting their maturation / Alimohammadi Shahrzad, Pénzes Zsófia, Horváth Dorottya, Gyetvai Ágnes, Bácsi Attila, Kis Nikoletta Gréta, Németh Ákos, Arany József, Oláh Attila, Lisztes Erika, Tóth Balázs István, Bíró Tamás, Szöllősi Attila Gábor
Dátum:2023
ISSN:0022-202X 1523-1747
Megjegyzések:Langerhans cells (LCs) are the sole professional antigen-presenting cell normally found in the human epidermal compartment. Research into their physiological role is hindered by the fact that they are invariably activated during isolation from the skin. To overcome this challenge, we turned to a monocyte-derived LC model (moLC), which we characterized with RNASeq, and compared the transcriptome of moLCs to donor-matched immature dendritic cells. We found that moLCs express markers characteristic of LC2 cells, as well as transient receptor potential vanilloid 4 (TRPV4). TRPV4 is especially important in skin, as it has been linked to conservation of the skin barrier, immunological responses as well as acute and chronic itch, but we know little about its function on LCs. Our results show that TRPV4 activation increased the expression of Langerin and led to increased intracellular calcium concentration in moLCs. Regarding the functionality of moLCs, we found that TRPV4 agonism had a mitigating effect on their inflammatory responses, since it decreased their cytokine production, and T cell activating capability. As TRPV4 has emerged as a potential therapeutic target in dermatological conditions, it is important to highlight LCs as a novel target of these therapies.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Langerhans sejt
Dendritikus sejt
Immunológia
Természetes immunitás
Megjelenés:Journal Of Investigative Dermatology. - 143 : 5 (2023), p. 801-811.e10. -
További szerzők:Pénzes Zsófia (1992-) (klinikai laboratóriumi kutató) Horváth Dorottya (1994-) (molekuláris biológus) Gyetvai Ágnes Bácsi Attila (1967-) (immunológus) Kis Gréta (1979-) (környezetkutató) Németh Ákos (1984-) (gyógyszer-vegyészmérnök, közgazdász) Arany József (1990-) (klinikai laboratóriumi kutató, vegyész) Oláh Attila (1984-) (élettanász) Lisztes Erika (1986-) (élettanász) Tóth István Balázs (1978-) (élettanász) Bíró Tamás (1968-) (élettanász) Szöllősi Attila Gábor (1982-) (élettanász)
Pályázati támogatás:125053
OTKA
128034
OTKA
134235
OTKA
GINOP-2.3.2-15-2016-00015
GINOP
GINOP-2.3.3-15-2016-00020
GINOP
EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
MTA-DE
MTA
Internet cím:Szerző által megadott URL
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Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM114466
035-os BibID:(Scopus)85169695767 (cikkazonosító)1240800 (WOS)001058511200001
Első szerző:Pénzes Zsófia (klinikai laboratóriumi kutató)
Cím:The dual role of cannabidiol on monocyte-derived dendritic cell differentiation and maturation / Zsófia Pénzes, Shahrzad Alimohammadi, Dorottya Horváth, Attila Oláh, Balázs István Tóth, Attila Bácsi, Attila Gábor Szöllősi
Dátum:2023
ISSN:1664-3224
Megjegyzések:Introduction: Extracts and compounds isolated from hemp (Cannabis sativa) are increasingly gaining popularity in the treatment of a number of diseases, with topical formulations for dermatological conditions leading the way. Phytocannabinoids such as ( )-cannabidiol, ( )-cannabinol and ( )-?9-tetrahydrocannabivarin (CBD, CBN, and THCV, respectively), are present in variable amounts in the plant, and have been shown to have mostly anti-inflammatory effects both in vitro and in vivo, albeit dominantly in murine models. The role of phytocannabinoids in regulating responses of dendritic cells (DCs) remains unclear. Methods: Our research aimed to investigate the effects of CBD, CBN, and THCV on human DCs differentiated from monocytes (moDCs). moDCs were treated with up to 10 ?M of each phytocannabinoid, and their effects on viability, differentiation, and maturation were assessed both alone, and in conjunction with TLR agonists. The effects of CBD on cytokine production, T cell activation and polarization as well as the transcriptome of moDCs was also determined. Results: Phytocannabinoids did not influence the viability of moDCs up to 10 ?M, and only CBD had effects on maturational markers of moDCs, and neither compound influenced LPS-induced activation at 10 ?M. Since only CBD had measurable effects on moDCs, in our subsequent experiments we tested the effect only of that pCB. On moDCs differentiated in the presence of CBD subsequent activation by LPS induced a markedly different, much more tolerogenic response. CBD-treated moDCs also produced significantly more interleukin (IL)-6, TNF? and, importantly, IL-10 in response to LPS, which shows a shift toward anti-inflammatory signaling, as well as a more robust secretory response in general. To rule out the possibility that these effects of CBD are specific to TLR4 signaling, we determined the effect of CBD on TLR7/8-induced maturation as well, and saw similar, although less marked responses. CBD-treated moDCs were also less efficient at activating naïve T cells after LPS stimulation, further supporting the tolerogenic effect of this phytocannabinoid on moDCs. Reactome pathway analysis showed an inflammatory response to LPS in moDCs, and to a lesser extent to CBD as well. In contrast CBD-treated moDCs responded to LPS with a shift towards a more tolerogenic phenotype, as IL-10 signaling was the most prominently induced pathway in this group. Discussion: Our results show that CBD achieves an anti-inflammatory effect on adaptive immune responses only in the presence of an activating stimuli on moDCs by reprogramming cells during long-term treatment, and not through acute, short-term effects.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
fitokannabinoidok
kannabidiol
monocita-eredetű dendritikus sejtek
veleszületett immunitás
T sejt proliferáció
Megjelenés:Frontiers in Immunology. - 14 (2023), p. 1240800. -
További szerzők:Alimohammadi, Shahrzad (1991-) (Gyógyszerész) Horváth Dorottya (1994-) (molekuláris biológus) Oláh Attila (1984-) (élettanász) Tóth István Balázs (1978-) (élettanász) Bácsi Attila (1967-) (immunológus) Szöllősi Attila Gábor (1982-) (élettanász)
Pályázati támogatás:128034
OTKA
134993
OTKA
134235
OTKA
134725
OTKA
GINOP-2.3.2-15-2016-00026
GINOP
GINOP-2.3.3-15-2016-00020
GINOP
EFOP-3.6.3-VEKOP-16-2017-00009
EFOP
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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