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...
| Main Authors: | , , , , , , , , |
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| פורמט: | Article |
| שפה: | Russian |
| יצא לאור: |
St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists
2019-12-01
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| סדרה: | Медицинская иммунология |
| נושאים: | |
| גישה מקוונת: | https://www.mimmun.ru/mimmun/article/view/1622 |
| _version_ | 1826534125297729536 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-08T05:48:32Z |
| format | Article |
| id | doaj.art-38cce2508915427fa7747eaaed410dbb |
| institution | Directory Open Access Journal |
| issn | 1563-0625 2313-741X |
| language | Russian |
| last_indexed | 2025-03-14T02:18:03Z |
| publishDate | 2019-12-01 |
| publisher | St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists |
| record_format | Article |
| series | Медицинская иммунология |
| spelling | doaj.art-38cce2508915427fa7747eaaed410dbb2025-03-11T17:59:10ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2019-12-0121583584610.15789/1563-0625-2019-5-835-8461146INFLUENCE OF DEXAMETHASONE-MODIFIED DENDRITIC CELLS GENERATED WITH IFNα UPON AUTOLOGOUS T LYMPHOCYTE FUNCTIONS IN THE PATIENTS WITH RHEUMATOID ARTHRITISYu. D. Kurochkina0T. V. Tyrinova1O. Yu. Leplina2M. A. Tikhonova3A. E. Sizikov4A. E. Sulutian5O. A. Chumasova6A. A. Ostanin7E. R. Chernykh8Institute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyDendritic 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.https://www.mimmun.ru/mimmun/article/view/1622dendritic cellsinterferon-αdexamethasoneauto-mlcapoptosisanergycytokinestr1rheumatoid arthritis |
| spellingShingle | 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 Медицинская иммунология dendritic cells interferon-α dexamethasone auto-mlc apoptosis anergy cytokines tr1 rheumatoid arthritis |
| title | 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_short | 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 |
| topic | dendritic cells interferon-α dexamethasone auto-mlc apoptosis anergy cytokines tr1 rheumatoid arthritis |
| url | https://www.mimmun.ru/mimmun/article/view/1622 |
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