INFLUENCE OF DEXAMETHASONE-MODIFIED DENDRITIC CELLS GENERATED WITH IFNα UPON AUTOLOGOUS T LYMPHOCYTE FUNCTIONS IN THE PATIENTS WITH RHEUMATOID ARTHRITIS

Dendritic cells (DCs) play a key role in maintaining the peripheral tolerance of lymphocytes to autoantigens. Recovery of immunological tolerance in autoimmune diseases, particularly, in rheumatoid arthritis (RA) is considered a new therapeutic strategy. The aim of this work was to study the effect...

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Autores principales:	Yu. D. Kurochkina, T. V. Tyrinova, O. Yu. Leplina, M. A. Tikhonova, A. E. Sizikov, A. E. Sulutian, O. A. Chumasova, A. A. Ostanin, E. R. Chernykh
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2019
Materias:	dendritic cells interferon-α dexamethasone auto-mlc apoptosis anergy cytokines tr1 rheumatoid arthritis Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/38cce2508915427fa7747eaaed410dbb
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spelling	oai:doaj.org-article:38cce2508915427fa7747eaaed410dbb2021-11-18T08:03:48ZINFLUENCE OF DEXAMETHASONE-MODIFIED DENDRITIC CELLS GENERATED WITH IFNα UPON AUTOLOGOUS T LYMPHOCYTE FUNCTIONS IN THE PATIENTS WITH RHEUMATOID ARTHRITIS1563-06252313-741X10.15789/1563-0625-2019-5-835-846https://doaj.org/article/38cce2508915427fa7747eaaed410dbb2019-12-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1622https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XDendritic cells (DCs) play a key role in maintaining the peripheral tolerance of lymphocytes to autoantigens. Recovery of immunological tolerance in autoimmune diseases, particularly, in rheumatoid arthritis (RA) is considered a new therapeutic strategy. The aim of this work was to study the effect of dexamethasone-modified DCs generated from monocytes of RA patients in the presence of IFNα (DCsDex), upon autologous T lymphocytes in mixed leukocyte culture (auto-MLC), and to investigate possible mechanisms of the DCsdex tolerogenic effect upon autoreactive T cells. We have shown, that DCsDex from RA patients induce T cell hyporeactivity in auto-MLC. Hyporeactivity of T cells is associated with cell cycle blockage in CD4+T lymphocytes and decreased IFNγ, IL-17, IL-4 and IL-13 production, which indicates the induction of CD4+T cell anergy. In this case, inhibition of Th1/Th17 has been more pronounced than the suppression of Th2 cells producing IL-4 and IL-13. Along with T cell anergy, the decrease of proliferative response in auto-MLC is associated with increased CD3+T lymphocyte apoptosis. In addition, the DCsDex of RA patients suppresses the proliferation of autologous T cells stimulated by unmodified DCs. This effect is associated with enhancement of IL-10-producing CD4+T cells in the auto-MLC, thus being indicative for an ability of DCsDex to induce conversion of CD4+T lymphocytes into regulatory T cells (Tr1). The data obtained characterize a new type of tolerogenic DCs, generated from blood monocytes of RA patients in the presence of IFNα and modified by dexamethasone, thus revealing a mechanism for tolerogenic effect of DCsDex upon T cells that recognize self-antigens in auto-MLC.Yu. D. KurochkinaT. V. TyrinovaO. Yu. LeplinaM. A. TikhonovaA. E. SizikovA. E. SulutianO. A. ChumasovaA. A. OstaninE. R. ChernykhSPb RAACIarticledendritic cellsinterferon-αdexamethasoneauto-mlcapoptosisanergycytokinestr1rheumatoid arthritisImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 21, Iss 5, Pp 835-846 (2019)
institution	DOAJ
collection	DOAJ
language	RU
topic	dendritic cells interferon-α dexamethasone auto-mlc apoptosis anergy cytokines tr1 rheumatoid arthritis Immunologic diseases. Allergy RC581-607
spellingShingle	dendritic cells interferon-α dexamethasone auto-mlc apoptosis anergy cytokines tr1 rheumatoid arthritis Immunologic diseases. Allergy RC581-607 Yu. D. Kurochkina T. V. Tyrinova O. Yu. Leplina M. A. Tikhonova A. E. Sizikov A. E. Sulutian O. A. Chumasova A. A. Ostanin E. R. Chernykh INFLUENCE OF DEXAMETHASONE-MODIFIED DENDRITIC CELLS GENERATED WITH IFNα UPON AUTOLOGOUS T LYMPHOCYTE FUNCTIONS IN THE PATIENTS WITH RHEUMATOID ARTHRITIS
description	Dendritic cells (DCs) play a key role in maintaining the peripheral tolerance of lymphocytes to autoantigens. Recovery of immunological tolerance in autoimmune diseases, particularly, in rheumatoid arthritis (RA) is considered a new therapeutic strategy. The aim of this work was to study the effect of dexamethasone-modified DCs generated from monocytes of RA patients in the presence of IFNα (DCsDex), upon autologous T lymphocytes in mixed leukocyte culture (auto-MLC), and to investigate possible mechanisms of the DCsdex tolerogenic effect upon autoreactive T cells. We have shown, that DCsDex from RA patients induce T cell hyporeactivity in auto-MLC. Hyporeactivity of T cells is associated with cell cycle blockage in CD4+T lymphocytes and decreased IFNγ, IL-17, IL-4 and IL-13 production, which indicates the induction of CD4+T cell anergy. In this case, inhibition of Th1/Th17 has been more pronounced than the suppression of Th2 cells producing IL-4 and IL-13. Along with T cell anergy, the decrease of proliferative response in auto-MLC is associated with increased CD3+T lymphocyte apoptosis. In addition, the DCsDex of RA patients suppresses the proliferation of autologous T cells stimulated by unmodified DCs. This effect is associated with enhancement of IL-10-producing CD4+T cells in the auto-MLC, thus being indicative for an ability of DCsDex to induce conversion of CD4+T lymphocytes into regulatory T cells (Tr1). The data obtained characterize a new type of tolerogenic DCs, generated from blood monocytes of RA patients in the presence of IFNα and modified by dexamethasone, thus revealing a mechanism for tolerogenic effect of DCsDex upon T cells that recognize self-antigens in auto-MLC.
format	article
author	Yu. D. Kurochkina T. V. Tyrinova O. Yu. Leplina M. A. Tikhonova A. E. Sizikov A. E. Sulutian O. A. Chumasova A. A. Ostanin E. R. Chernykh
author_facet	Yu. D. Kurochkina T. V. Tyrinova O. Yu. Leplina M. A. Tikhonova A. E. Sizikov A. E. Sulutian O. A. Chumasova A. A. Ostanin E. R. Chernykh
author_sort	Yu. D. Kurochkina
title	INFLUENCE OF DEXAMETHASONE-MODIFIED DENDRITIC CELLS GENERATED WITH IFNα UPON AUTOLOGOUS T LYMPHOCYTE FUNCTIONS IN THE PATIENTS WITH RHEUMATOID ARTHRITIS
title_short	INFLUENCE OF DEXAMETHASONE-MODIFIED DENDRITIC CELLS GENERATED WITH IFNα UPON AUTOLOGOUS T LYMPHOCYTE FUNCTIONS IN THE PATIENTS WITH RHEUMATOID ARTHRITIS
title_full	INFLUENCE OF DEXAMETHASONE-MODIFIED DENDRITIC CELLS GENERATED WITH IFNα UPON AUTOLOGOUS T LYMPHOCYTE FUNCTIONS IN THE PATIENTS WITH RHEUMATOID ARTHRITIS
title_fullStr	INFLUENCE OF DEXAMETHASONE-MODIFIED DENDRITIC CELLS GENERATED WITH IFNα UPON AUTOLOGOUS T LYMPHOCYTE FUNCTIONS IN THE PATIENTS WITH RHEUMATOID ARTHRITIS
title_full_unstemmed	INFLUENCE OF DEXAMETHASONE-MODIFIED DENDRITIC CELLS GENERATED WITH IFNα UPON AUTOLOGOUS T LYMPHOCYTE FUNCTIONS IN THE PATIENTS WITH RHEUMATOID ARTHRITIS
title_sort	influence of dexamethasone-modified dendritic cells generated with ifnα upon autologous t lymphocyte functions in the patients with rheumatoid arthritis
publisher	SPb RAACI
publishDate	2019
url	https://doaj.org/article/38cce2508915427fa7747eaaed410dbb
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INFLUENCE OF DEXAMETHASONE-MODIFIED DENDRITIC CELLS GENERATED WITH IFNα UPON AUTOLOGOUS T LYMPHOCYTE FUNCTIONS IN THE PATIENTS WITH RHEUMATOID ARTHRITIS

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