IFNα-INDUCED DENDRITIC CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND THEIR SENSITIVITY TO DEXAMETHASONE

Dendritic cells (DCs) play an important role in pathogenesis of rheumatoid arthritis (RA) and are considered a novel target for immune therapy. Under inflammatory conditions, local dendritic cells of non-lymphoid organs are thought to be differentiated from monocytes. Moreover, DCs differentiation a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	E. R. Chernykh, Yu. D. Kurochkina, O. Yu. Leplina, M. A. Tikhonova, T. V. Tyrinova, A. E. Sizikov, O. A. Chumasova, A. A. Ostanin
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2017
Materias:	dendritic cells interferon-α dexamethasone allo-mlc cytokines rheumatoid arthritis Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/790332e5b53346baac5c647f7275742e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:790332e5b53346baac5c647f7275742e
record_format	dspace
spelling	oai:doaj.org-article:790332e5b53346baac5c647f7275742e2021-11-18T08:03:46ZIFNα-INDUCED DENDRITIC CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND THEIR SENSITIVITY TO DEXAMETHASONE1563-06252313-741X10.15789/1563-0625-2017-3-255-266https://doaj.org/article/790332e5b53346baac5c647f7275742e2017-07-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1259https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XDendritic cells (DCs) play an important role in pathogenesis of rheumatoid arthritis (RA) and are considered a novel target for immune therapy. Under inflammatory conditions, local dendritic cells of non-lymphoid organs are thought to be differentiated from monocytes. Moreover, DCs differentiation and activation in RA may be largely controlled by interferon-alpha. The aim of the present study was to investigate phenotypic and functional properties of monocyte-derived DCs generated in the presence of interferonalpha (IFN-DCs) in RA patients, and to specify, whether IFN-DCs are sensitive to a tolerogenic effect of dexamethasone. Fourteen RA patients with moderate-to-high disease activity treated with disease-modifying drugs have been included into the study. Twenty sex- and age-related healthy donors were used as a control. IFN-DCs were generated from monocytes by culturing adherent fraction of mononuclear cells for 5 days with GM-CSF and IFNα in the absence or presence of dexamethasone (10-6 M). IFN-DCs from RA patients were characterized by increased numbers of CD14+CD83- and lower amounts of CD14- CD83+ cells, thus presuming a delayed maturation. Furthermore, IFN-DCs from patients were characterized by higher expression of B7-H1 and TLR2. The phenotypic changes did not significantly influence specific functional activities of DCs, in particular, the capacity of DCs to produce TNFα, IL-10, IL-6, to stimulate proliferation of allogeneic T-cells and to activate T-cells for Th1 and Th2 cytokine production. Generation of patients’ DCs in presence of dexamethasone caused a decrease in CD83 and CD86 expression, reduced TNFα production, and suppressed allostimulatory activity of the DCs. Moreover, dexamethasone inhibited the ability of DC to stimulate Th1 response, along with shifting the balance towards Th2-stimulating activity. The data obtained provide an evidence that IFN-DCs from RA patients remain sensitive to the tolerogenic effects of dexamethasone. Furthermore, the revealed variations in sensitivity of patient’s DCs to dexamethasone-mediated inhibitory effect may be of interest for prediction of therapeutic response to glucocorticoid therapy. Our results also provide an evidence for possible implementation of IFN-DCs as a new cell platform for obtaining tolerogenic DCs.E. R. ChernykhYu. D. KurochkinaO. Yu. LeplinaM. A. TikhonovaT. V. TyrinovaA. E. SizikovO. A. ChumasovaA. A. OstaninSPb RAACIarticledendritic cellsinterferon-αdexamethasoneallo-mlccytokinesrheumatoid arthritisImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 19, Iss 3, Pp 255-266 (2017)
institution	DOAJ
collection	DOAJ
language	RU
topic	dendritic cells interferon-α dexamethasone allo-mlc cytokines rheumatoid arthritis Immunologic diseases. Allergy RC581-607
spellingShingle	dendritic cells interferon-α dexamethasone allo-mlc cytokines rheumatoid arthritis Immunologic diseases. Allergy RC581-607 E. R. Chernykh Yu. D. Kurochkina O. Yu. Leplina M. A. Tikhonova T. V. Tyrinova A. E. Sizikov O. A. Chumasova A. A. Ostanin IFNα-INDUCED DENDRITIC CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND THEIR SENSITIVITY TO DEXAMETHASONE
description	Dendritic cells (DCs) play an important role in pathogenesis of rheumatoid arthritis (RA) and are considered a novel target for immune therapy. Under inflammatory conditions, local dendritic cells of non-lymphoid organs are thought to be differentiated from monocytes. Moreover, DCs differentiation and activation in RA may be largely controlled by interferon-alpha. The aim of the present study was to investigate phenotypic and functional properties of monocyte-derived DCs generated in the presence of interferonalpha (IFN-DCs) in RA patients, and to specify, whether IFN-DCs are sensitive to a tolerogenic effect of dexamethasone. Fourteen RA patients with moderate-to-high disease activity treated with disease-modifying drugs have been included into the study. Twenty sex- and age-related healthy donors were used as a control. IFN-DCs were generated from monocytes by culturing adherent fraction of mononuclear cells for 5 days with GM-CSF and IFNα in the absence or presence of dexamethasone (10-6 M). IFN-DCs from RA patients were characterized by increased numbers of CD14+CD83- and lower amounts of CD14- CD83+ cells, thus presuming a delayed maturation. Furthermore, IFN-DCs from patients were characterized by higher expression of B7-H1 and TLR2. The phenotypic changes did not significantly influence specific functional activities of DCs, in particular, the capacity of DCs to produce TNFα, IL-10, IL-6, to stimulate proliferation of allogeneic T-cells and to activate T-cells for Th1 and Th2 cytokine production. Generation of patients’ DCs in presence of dexamethasone caused a decrease in CD83 and CD86 expression, reduced TNFα production, and suppressed allostimulatory activity of the DCs. Moreover, dexamethasone inhibited the ability of DC to stimulate Th1 response, along with shifting the balance towards Th2-stimulating activity. The data obtained provide an evidence that IFN-DCs from RA patients remain sensitive to the tolerogenic effects of dexamethasone. Furthermore, the revealed variations in sensitivity of patient’s DCs to dexamethasone-mediated inhibitory effect may be of interest for prediction of therapeutic response to glucocorticoid therapy. Our results also provide an evidence for possible implementation of IFN-DCs as a new cell platform for obtaining tolerogenic DCs.
format	article
author	E. R. Chernykh Yu. D. Kurochkina O. Yu. Leplina M. A. Tikhonova T. V. Tyrinova A. E. Sizikov O. A. Chumasova A. A. Ostanin
author_facet	E. R. Chernykh Yu. D. Kurochkina O. Yu. Leplina M. A. Tikhonova T. V. Tyrinova A. E. Sizikov O. A. Chumasova A. A. Ostanin
author_sort	E. R. Chernykh
title	IFNα-INDUCED DENDRITIC CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND THEIR SENSITIVITY TO DEXAMETHASONE
title_short	IFNα-INDUCED DENDRITIC CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND THEIR SENSITIVITY TO DEXAMETHASONE
title_full	IFNα-INDUCED DENDRITIC CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND THEIR SENSITIVITY TO DEXAMETHASONE
title_fullStr	IFNα-INDUCED DENDRITIC CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND THEIR SENSITIVITY TO DEXAMETHASONE
title_full_unstemmed	IFNα-INDUCED DENDRITIC CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND THEIR SENSITIVITY TO DEXAMETHASONE
title_sort	ifnα-induced dendritic cells in patients with rheumatoid arthritis and their sensitivity to dexamethasone
publisher	SPb RAACI
publishDate	2017
url	https://doaj.org/article/790332e5b53346baac5c647f7275742e
work_keys_str_mv	AT erchernykh ifnainduceddendriticcellsinpatientswithrheumatoidarthritisandtheirsensitivitytodexamethasone AT yudkurochkina ifnainduceddendriticcellsinpatientswithrheumatoidarthritisandtheirsensitivitytodexamethasone AT oyuleplina ifnainduceddendriticcellsinpatientswithrheumatoidarthritisandtheirsensitivitytodexamethasone AT matikhonova ifnainduceddendriticcellsinpatientswithrheumatoidarthritisandtheirsensitivitytodexamethasone AT tvtyrinova ifnainduceddendriticcellsinpatientswithrheumatoidarthritisandtheirsensitivitytodexamethasone AT aesizikov ifnainduceddendriticcellsinpatientswithrheumatoidarthritisandtheirsensitivitytodexamethasone AT oachumasova ifnainduceddendriticcellsinpatientswithrheumatoidarthritisandtheirsensitivitytodexamethasone AT aaostanin ifnainduceddendriticcellsinpatientswithrheumatoidarthritisandtheirsensitivitytodexamethasone
_version_	1718422361355583488

IFNα-INDUCED DENDRITIC CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND THEIR SENSITIVITY TO DEXAMETHASONE

Ejemplares similares