scholarly journals Dendritic cells, T cells and their interaction in rheumatoid arthritis

2019 ◽  
Vol 196 (1) ◽  
pp. 12-27 ◽  
Author(s):  
P. Wehr ◽  
H. Purvis ◽  
S.‐C. Law ◽  
R. Thomas
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Dendritic Cells

Synovial Dendritic Cells and T Cells in Rheumatoid Arthritis

1988 ◽  
Vol 17 (sup74) ◽  
pp. 79-88 ◽  
Author(s):  
Van Tsai ◽  
Ville Bergroth ◽  
Nathan J. Zvaifler
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Dendritic Cells

Dendritic cells and T cells in rheumatoid arthritis

2020 ◽  
pp. 73-84
Author(s):  
Soi-Cheng Law ◽  
Pascale Wehr ◽  
Harriet Purvis ◽  
Ranjeny Thomas
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Dendritic Cells ◽  
Autoimmune Response ◽  
Immune Effector ◽  
Effector Functions ◽  
Adaptive Immune ◽  
Cell Antibody ◽  
Innate Immune Effector ◽  
Antigen Presenting

Dendritic cells (DCs) are specialized antigen-presenting cells which link the innate and adaptive immune responses, activating and priming effector CD4+ T cells, cross-presenting antigen to CD8+ T cells, and promoting B-cell antibody production. DCs also play important roles in the maintenance of immune tolerance. DCs and T cells underpin the basis of the autoimmune response in rheumatoid arthritis. In this chapter we describe the function of DCs and the response of T cells in rheumatoid arthritis pathogenesis, introduce the DC and T-cell players and their function in the immune system, then review the evidence for their involvement in the pathogenesis of rheumatoid arthritis (RA), particularly through the presentation of antigen that triggers the differentiation of autoreactive T cells, as well as innate immune effector functions. Finally, the emerging prospects for DC targeting for immunotherapy are covered.

scholarly journals Thymic Stromal Lymphopoietin, a Novel Proinflammatory Mediator in Rheumatoid Arthritis That Potently Activates CD1c+ Myeloid Dendritic Cells to Attract and Stimulate T Cells

2014 ◽  
Vol 66 (5) ◽  
pp. 1176-1184 ◽  
Author(s):  
Frederique M. Moret ◽  
Cornelis E. Hack ◽  
Kim M. G. van der Wurff-Jacobs ◽  
Timothy R. D. J. Radstake ◽  
Floris P. J. G. Lafeber ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Dendritic Cells ◽  
Thymic Stromal Lymphopoietin ◽  
Myeloid Dendritic Cells ◽  
Proinflammatory Mediator

scholarly journals POS0367 NLRC4 AND FC-γ-R CROSSTALK ON CD1C+ DENDRITIC CELLS DIFFERENTIALLY CONTRIBUTES TO RHEUMATOID ARTHRITIS IMMUNOPATHOLOGY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 413.2-413
Author(s):  
C. Delgado-Arévalo ◽  
M. Calvet-Mirabent ◽  
A. Triguero-Martinez ◽  
E. Vazquez de Luis ◽  
A. Benguría-Filippini ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Dendritic Cells ◽  
Synovial Fluid ◽  
Cd4 T Cells ◽  
Treatment Initiation ◽  
Fc Receptor ◽  
Response To Therapy ◽  
Caspase 1

Background:Rheumatoid arthritis (RA) is an autoimmune disorder in which Th17 cells, B cells and inflammatory cytokines (1-3) contribute to joint tissue damage, however the role of specific myeloid populations to immunopathogenesis of RA remains unclear.Objectives:To address this question, we studied transcriptional, phenotypical and functional characteristics of monocytes (Mo), CD1c+ and CD141+ conventional dendritic cells (cDC) from RA patients.Methods:Frequencies and maturation patterns of Lin-CD14-HLADR+ plasmacytoid (CD11c-), CD1c+ and CD141+ cDC (CD11c+) subsets and CD14+ Mo from n=25 RA patients at baseline were analyzed by multicolor flow cytometry. In addition, longitudinal studies on the evolution of these populations after treatment initiation were conducted on a smaller group of RA patients. Moreover, CD1c+ and CD141+ cDC subsets and total Mo were sorted from the peripheral blood from n=4 untreated RA and healthy individuals and the synovial fluid from n=3 RA and chondrocalcinosis patients. Differential transcriptional patterns within each population were analyzed by RNAseq. Functional validation of targets were performed in vitro with cDC subsets isolated form the synoviual fluid of RA patients. Finally, silencing of expression of NLRC4 and NLRP3 on CD1c+cDCs was performed with specific siRNAs.Results:Both CD1c+ (p=0.0001) and CD141+ (p=0.0008) cDCs were significantly depleted from the blood and enriched in the synovial fluid from untreated RA patients, but proportions of CD1c+ cDCs were more significantly recovered after treatment initiation and associated with improved clinical parameters. In addition, specific increased expression levels of the IgG-Fc receptor CD64 on CD1c+ cDC was associated with higher DAS28 (p=0.0002). Moreover, differential transcriptional patterns of circulating CD1c+cDCs from RA patients were characterized by genes linked to toll-like receptor, Fc-receptor, inflammasome pathways and elevated CCR2 expression (p=0.016), while CD141+cDCs transcribed interferon-related genes. Importantly, CCR2+ CD64Hi CD1c+cDCs from the synovial fluid from RA patients transcribed proinflammatory cytokines such as IL1-β, CCL3 and IL-8, actively expressed the inflammasome mediator caspase 1 and were more effective activating pathogenic IFNγ+IL-17+ CD4+ T cells in vitro than CD141+ cDC (p=0.0019). These functional profiles could be artificially induced stimulating CD1c+ cDCs with dsDNA in the presence of IgGs and was dependent on caspase 1 and the NLRC4 inflammasome.Conclusion:Our data provides novel insights about specific activation and functional patterns on CD1c+cDC contributing to RA pathogenesis and identifies new sensors that could represent novel therapeutic target to treat RA.References:[1]Alvandpur N, Tabatabaei R, Tahamoli-Roudsari A, Basiri Z, Behzad M, Rezaeepoor M, et al. Circulating IFN-gamma producing CD4+ T cells and IL-17A producing CD4+ T cells, HLA-shared epitope and ACPA may characterize the clinical response to therapy in rheumatoid arthritis patients. Human immunology. 2020.[2]Nistala K, Adams S, Cambrook H, Ursu S, Olivito B, de Jager W, et al. Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(33):14751-6.[3]Chapuy-Regaud S, Nogueira L, Clavel C, Sebbag M, Vincent C, Serre G. IgG subclass distribution of the rheumatoid arthritis-specific autoantibodies to citrullinated fibrin. Clinical and experimental immunology. 2005;139(3):542-50.Disclosure of Interests:None declared

scholarly journals Dopamine as an immune-modulator between dendritic cells and T cells and the role of dopamine in the pathogenesis of Rheumatoid Arthritis

2009 ◽  
Vol 32 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Kazuhisa NAKANO ◽  
Sho MATSUSHITA ◽  
Kazuyoshi SAITO ◽  
Kunihiro YAMAOKA ◽  
Yoshiya TANAKA
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune Modulator

scholarly journals Generation and characterisation of therapeutic tolerogenic dendritic cells for rheumatoid arthritis

2010 ◽  
Vol 69 (11) ◽  
pp. 2042-2050 ◽  
Author(s):  
Rachel A Harry ◽  
Amy E Anderson ◽  
John D Isaacs ◽  
Catharien M U Hilkens
Keyword(s):  
Rheumatoid Arthritis ◽  
Quality Control ◽  
T Cells ◽  
Dendritic Cells ◽  
Experimental Treatment ◽  
Immunosuppressive Drugs ◽  
Interleukin 17 ◽  
Proinflammatory Mediators ◽  
Monophosphoryl Lipid A ◽  
Tolerogenic Dendritic Cells

ObjectivesTolerogenic dendritic cells (tolDCs) constitute a promising experimental treatment for targeting autoreactive T cells in autoimmune diseases, including rheumatoid arthritis (RA). The authors' goal is to bring tolDC therapy for RA to the clinic. Here the authors address key translational issues related to the manufacturing of tolDCs from RA patients with current good manufacturing practice (cGMP)-compliant reagents, the stability of tolDCs, and the selection of suitable quality control markers.MethodsHuman monocyte-derived tolDCs were established from RA patients and healthy controls (HCs) using the immunosuppressive drugs dexamethasone and vitamin D3, and the cGMP-grade immunomodulator, monophosphoryl lipid A, in the cGMP-compliant medium, CellGroDC. The functionality of tolDCs and tolDC-modulated autologous CD4 T cells was determined by flow cytometry, [3H]thymidine incorporation and ELISA.ResultsClinical-grade tolDCs established from patients with RA exhibit a typical tolerogenic phenotype of reduced costimulatory molecules, low production of proinflammatory cytokines and impaired stimulation of autologous antigen-specific T cells, comparable to HC tolDCs. Toll-like receptor 2 (TLR-2) was highly expressed by tolDCs but not mature DCs. Furthermore, tolDCs suppressed mature DC-induced T cell proliferation, interferon γ and interleukin 17 production, and rendered T cells hyporesponsive to further stimulation. Importantly, tolDCs were phenotypically stable in the absence of immunosuppressive drugs and were refractory to further challenge with proinflammatory mediators.ConclusionstolDCs established from patients with RA are comparable to those derived from healthy donors. TLR-2 was identified as an ideal marker for quality control of tolDCs. Potently tolerogenic and highly stable, these tolDCs are a promising cellular therapeutic for tailored immunomodulation in the treatment of RA.

scholarly journals POS0673 TOLEROGENIC DENDRITIC CELLS IN RHEUMATOID ARTHRITIS PATIENTS: NEWS AND PROMISES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 581.2-581
Author(s):  
Y. Kurochkina ◽  
E. Chernykh ◽  
A. Sizikov
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Dendritic Cells ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Moderate Activity ◽  
Blood Monocytes ◽  
Gm Csf ◽  
Hla Dr ◽  
Enhanced Expression

Background:Dendritic cells (DCs) are known to contribute to the pathogenesis of rheumatoid arthritis (RA) through presentation of cartilage glycoprotein, production of proinflammatory cytokines and activation of Th1/Th17 responses. Along with stimulating activity, DCs may exhibit suppressive functions via capacity to induce T cell apoptosis/anergy and to generate regulatory T cells. Since these DCs have potential to control autoreactive T-lymphocytes, the enhancing of tolerogenic properties of DCs seems to be a new important strategy in treatment of RA. Dexamethasone is widely used in clinical practice and can be used as a tolerogenic substance. Therefore, the properties of DCs generated in presence of dexamethasone are of great clinical interests.Objectives:The aim of our study is to describe the properties of tolerogenic DCs, generated with dexamethasone in patients with RA and their influence on autologous T-cells.Methods:Sixty five patients with RA with high and moderate activity of disease were recruited in this study. All patients follow ACR/EULAR criteria (2010). All studies were performed after receiving informed consent. All patients received conventional synthetic DMARDs. DCs were generated from blood monocytes culturing for 5 days with GM-CSF and IFN-α in the presence dexamethasone (dexDCS), applied on third day. LPS as maturation stimuli was added on fourth day. The expression of CD14, CD83, HLA-DR, TLR-2 on the surface of DCs was measured by flow cytometry. The functions of DCs were evaluated by measuring cytokine production and DCs allostimulatory activity in mixed lymphocyte culture. Mature DCs generated in absence of dexamethasone used as control.Results:We revealed that dexDCs are characterized by enhanced expression of CD14+cells and decreased number of CD83+cells but percent of HLA-DR+cells were constant (about 85). DexDCs show high expression of TLR-2 is seen as tolerogenic molecule (75%vs51%, p=0.05 compared to control). DexDCs also have marked prominent increase of TNFα/IL-10 ratio in contrast to control (0.59 vs 1.8, p=0.03). DexDCs suppressed proliferation of allogenic T-cells (2005 vs 7980 cpm, p=0.0002). To assess the stability of the DC in the proinfflamatory micro-environment after assessing stimulatory activity dexDCs were then cultivated with LPS and allostimulatory activity were evaluated one more. The stimulation activity dexDCs after incubation with LPS were not increase (4692 vs 6053 cpm, p=0.7). Also earlier we showed possibility of dexDCs induse apoptosis of autologous T-cells, activation of CD4+IL10+Tr1 and possession of antigen-specific suppression.Conclusion:The data obtained indicate that dexDCs from RA patients have the main tolerogenic features and stable in inflammatory environment that proves their potential in the treatment of rheumatoid arthritis.Disclosure of Interests:None declared

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