Sergey V Sennikov1, Svetlana A Falaleeva2, Nadezhda S Shkaruba3, Oksana A Chumasova4, Irina A Obleukhova5, Aleksey E Sizikov6, Vasily V Kurilin7. 1. Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology" RIFCI, 14, Yadrincevskaya Str., Novosibirsk 630099, Russia. Electronic address: sennikovsv@gmail.com. 2. Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology" RIFCI, 14, Yadrincevskaya Str., Novosibirsk 630099, Russia. Electronic address: kolenteonok@sibmail.com. 3. Rheumatology Department, Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology" RIFCI, 14, Yadrincevskaya Str., Novosibirsk 630099, Russia. Electronic address: sen-nadezhda@yandex.ru. 4. Rheumatology Department, Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology" RIFCI, 14, Yadrincevskaya Str., Novosibirsk 630099, Russia. Electronic address: chumoks@mail.ru. 5. Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology" RIFCI, 14, Yadrincevskaya Str., Novosibirsk 630099, Russia. Electronic address: obleukhova.irina@yandex.ru. 6. Rheumatology Department, Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology" RIFCI, 14, Yadrincevskaya Str., Novosibirsk 630099, Russia. Electronic address: depaidici@online.nsk.su. 7. Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology" RIFCI, 14, Yadrincevskaya Str., Novosibirsk 630099, Russia. Electronic address: 2221910@ngs.ru.
Abstract
BACKGROUND: Since dendritic cells (DC) are involved in the development of autoimmune inflammation, researchers consider DC both as target cells for specific therapy of rheumatoid arthritis (RA) and as candidate cells for the development of cell-based methods to treat autoimmune diseases. The development of treatment strategies requires comprehensive research into the quantitative and qualitative characteristics of DC subtypes both ex vivo from RA patients and in vitro, to determine the possibility of inducing functionally mature DC in RA. OBJECTIVE: To study the phenotypic and functional properties of myeloid (mDC) and plasmacytoid (pDC) DC isolated from the peripheral blood of patients with RA and induced in vitro. MATERIALS AND METHODS: Blood samples were obtained from RA patients and healthy donors. Immature DC in the whole blood and in vitro induced DC were characterized by the positive expression of CD80, CD83, CCR7, IL-10, IL-4, IL-12 and IFN-α. R848 and lipopolysaccharide were used to determine DC maturation ability. From PBMCs of RA patients and health donors DCs with myeloid (imDC) and plasmacytoid (ipDC) phenotype were induced. RESULTS: The relative count of mDC in the peripheral blood between studied groups did not differ. pDC count was significantly lower for RA patients. DC from RA patients were characterized by low expression levels of CD80 and CD83 on both populations cells and high expression of CCR7 only on pDC. An increase in pDC producing IL-12 and IFN-α and a decrease in mDC and pDC producing IL-4 and IL-10 were shown in RA. imDC and ipDC obtained from RA patients according to their phenotype and cytokine profile did not differ from those obtained from healthy donors. CONCLUSIONS: There is an imbalance between subpopulations of DC in the peripheral blood of RA patients. DC of RA patients are less mature. The data suggest the involvement of DC in RA pathogenesis and confirm DC participation in balance shift towards Th1-type immune responses. At the same time, in vitro induced RA DC are phenotypically and functionally competent.
BACKGROUND: Since dendritic cells (DC) are involved in the development of autoimmune inflammation, researchers consider DC both as target cells for specific therapy of rheumatoid arthritis (RA) and as candidate cells for the development of cell-based methods to treat autoimmune diseases. The development of treatment strategies requires comprehensive research into the quantitative and qualitative characteristics of DC subtypes both ex vivo from RApatients and in vitro, to determine the possibility of inducing functionally mature DC in RA. OBJECTIVE: To study the phenotypic and functional properties of myeloid (mDC) and plasmacytoid (pDC) DC isolated from the peripheral blood of patients with RA and induced in vitro. MATERIALS AND METHODS: Blood samples were obtained from RApatients and healthy donors. Immature DC in the whole blood and in vitro induced DC were characterized by the positive expression of CD80, CD83, CCR7, IL-10, IL-4, IL-12 and IFN-α. R848 and lipopolysaccharide were used to determine DC maturation ability. From PBMCs of RApatients and health donors DCs with myeloid (imDC) and plasmacytoid (ipDC) phenotype were induced. RESULTS: The relative count of mDC in the peripheral blood between studied groups did not differ. pDC count was significantly lower for RApatients. DC from RApatients were characterized by low expression levels of CD80 and CD83 on both populations cells and high expression of CCR7 only on pDC. An increase in pDC producing IL-12 and IFN-α and a decrease in mDC and pDC producing IL-4 and IL-10 were shown in RA. imDC and ipDC obtained from RApatients according to their phenotype and cytokine profile did not differ from those obtained from healthy donors. CONCLUSIONS: There is an imbalance between subpopulations of DC in the peripheral blood of RApatients. DC of RApatients are less mature. The data suggest the involvement of DC in RA pathogenesis and confirm DC participation in balance shift towards Th1-type immune responses. At the same time, in vitro induced RADC are phenotypically and functionally competent.
Authors: Faye A H Cooles; Amy E Anderson; Andrew Skelton; Arthur G Pratt; Mariola S Kurowska-Stolarska; Iain McInnes; Catharien M U Hilkens; John D Isaacs Journal: Front Immunol Date: 2018-05-09 Impact factor: 7.561
Authors: Robin H G A van den Biggelaar; Ger J A Arkesteijn; Victor P M G Rutten; Willem van Eden; Christine A Jansen Journal: Front Immunol Date: 2020-02-26 Impact factor: 7.561