6 results on '"van Roon JA"'
Search Results
2. Association of Increased Treg Cell Levels With Elevated Indoleamine 2,3-Dioxygenase Activity and an Imbalanced Kynurenine Pathway in Interferon-Positive Primary Sjögren's Syndrome.
- Author
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Maria NI, van Helden-Meeuwsen CG, Brkic Z, Paulissen SM, Steenwijk EC, Dalm VA, van Daele PL, Martin van Hagen P, Kroese FG, van Roon JA, Harkin A, Dik WA, Drexhage HA, Lubberts E, and Versnel MA
- Subjects
- Female, Humans, Male, Middle Aged, Signal Transduction, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Interferons blood, Kynurenine physiology, Sjogren's Syndrome blood, Sjogren's Syndrome immunology, T-Lymphocytes, Regulatory enzymology
- Abstract
Objective: Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme that converts tryptophan to kynurenine, is driven in part by type I and type II interferons (IFNs). Naive T cells are polarized into FoxP3+ Treg cells upon exposure to either IDO+ cells or kynurenine. Recent studies have suggested that the kynurenine pathway reflects a crucial interface between the immune and nervous system. The aims of the present study were to evaluate whether Treg cell levels are elevated, in conjunction with increased IDO activity, in patients with primary Sjögren's syndrome (SS) who are positive for the IFN gene expression signature, and to investigate the downstream kynurenine pathway in these patients., Methods: Serum from 71 healthy controls, 58 IFN-negative patients with primary SS, and 66 IFN-positive patients with primary SS was analyzed using high-performance liquid chromatography to measure the levels of tryptophan and kynurenine. Expression levels of messenger RNA (mRNA) for IDO and downstream enzymes in the kynurenine pathway were assessed in CD14+ monocytes using real-time quantitative polymerase chain reaction. CD4+CD45RO+ T helper memory cell populations were analyzed by flow cytometry., Results: Significantly increased levels of IDO activity (assessed as the kynurenine:tryptophan ratio) (P = 0.0054) and percentages of CD25(high) FoxP3+ Treg cells (P = 0.039) were observed in the serum from IFN-positive patients with primary SS, and these parameters were significantly correlated with one another (r = 0.511, P = 0.002). In circulating monocytes from IFN-positive patients with primary SS, the expression of IDO1 mRNA was up-regulated (P < 0.0001), and this was correlated with the IFN gene expression score (r = 0.816, P < 0.0001). Interestingly, the proapoptotic and neurotoxic downstream enzyme kynurenine 3-monooxygenase was up-regulated (P = 0.0057), whereas kynurenine aminotransferase I (KATI) (P = 0.0003), KATIII (P = 0.016), and KATIV (P = 0.04) were down-regulated in IFN-positive patients with primary SS compared to healthy controls., Conclusion: These findings demonstrate enhanced IDO activity in conjunction with increased percentages of CD25(high) FoxP3+ Treg cells in primary SS patients who carry the IFN signature. In addition, IFN-positive patients with primary SS exhibit an imbalanced kynurenine pathway, with evidence of a shift toward potentially more proapoptotic and neurotoxic metabolites. Intervening in these IFN- and IDO-induced immune system imbalances may offer a new array of possibilities for therapeutic interventions in patients with primary SS., (© 2016, American College of Rheumatology.)
- Published
- 2016
- Full Text
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3. Low-Density Granulocytes Are Increased in Antiphospholipid Syndrome and Are Associated With Anti-β2 -Glycoprotein I Antibodies: Comment on the Article by Yalavarthi et al.
- Author
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van den Hoogen LL, Fritsch-Stork RD, van Roon JA, and Radstake TR
- Subjects
- Antibodies, Anticardiolipin, Antibodies, Antiphospholipid, Autoantibodies, Glycoproteins, Granulocytes, Humans, Antiphospholipid Syndrome, beta 2-Glycoprotein I
- Published
- 2016
- Full Text
- View/download PDF
4. Brief report: enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid.
- Author
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Leijten EF, van Kempen TS, Boes M, Michels-van Amelsfort JM, Hijnen D, Hartgring SA, van Roon JA, Wenink MH, and Radstake TR
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- Adult, Arthritis, Psoriatic metabolism, Arthritis, Rheumatoid metabolism, Arthritis, Rheumatoid pathology, CD146 Antigen metabolism, Case-Control Studies, Humans, Interleukin-17 metabolism, Lymphocytes metabolism, Middle Aged, Natural Cytotoxicity Triggering Receptor 2 metabolism, Receptors, CCR6 metabolism, Synovial Fluid metabolism, Arthritis, Psoriatic pathology, Immunity, Innate physiology, Lymphocytes pathology, Synovial Fluid cytology
- Abstract
Objective: Innate lymphoid cells (ILCs) are a recently discovered group of cells that are essential to epithelial homeostasis and are implicated in psoriasis pathogenesis, yet they have never been reported in psoriatic arthritis (PsA)., Methods: ILC classes and subsets were characterized in the peripheral blood (PB) of healthy controls, patients with psoriasis, and patients with PsA and in the synovial fluid (SF) of patients with PsA and patients with rheumatoid arthritis (RA). Cell surface marker expression and intracellular cytokine production following stimulation were analyzed using flow cytometry., Results: ILCs were identified in the SF and were 4-fold more abundant in PsA SF than in PsA PB. Fewer CCR6+ ILCs were found in PsA PB than in healthy control PB, while PsA SF was enriched for CCR6+ ILCs compared to PsA PB and RA SF. Natural cytotoxicity receptor NKp44+ group 3 ILCs were rare in PB and RA SF, but abundant in PsA SF. Increased numbers of interleukin-17A (IL-17A)-producing ILCs were present in PsA SF compared to RA SF. CCR6, NKp44, and melanoma cell adhesion molecule (MCAM) were expressed on the cell surface of SF ILCs that produced IL-17A. The number of circulating NKp44+, CCR6+, and MCAM+ ILCs in blood was inversely correlated with PsA disease activity., Conclusion: Our findings indicate that PsA SF is enriched for group 3 ILCs that express CCR6 and NKp44, which distinguishes the synovial compartment from RA. The increased IL-17A production by SF ILCs indicates a novel role for ILCs in PsA., (© 2015, American College of Rheumatology.)
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- 2015
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5. The efficacy of abatacept in reducing synovial T cell activation by CD1c myeloid dendritic cells is overruled by the stimulatory effects of T cell-activating cytokines.
- Author
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Moret FM, Bijlsma JW, Lafeber FP, and van Roon JA
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- Abatacept, Adult, Aged, Arthritis, Rheumatoid pathology, Cell Culture Techniques, Female, Flow Cytometry, Humans, Lymphocyte Activation immunology, Male, Middle Aged, Synovial Fluid cytology, Antigens, CD1 immunology, Arthritis, Rheumatoid immunology, CD4-Positive T-Lymphocytes immunology, Cytokines metabolism, Dendritic Cells immunology, Glycoproteins immunology, Immunoconjugates pharmacology, Immunosuppressive Agents pharmacology, Lymphocyte Activation drug effects
- Abstract
Objective: To investigate whether the potential of abatacept to inhibit vigorous CD1c myeloid dendritic cell (MDC)-driven activation of naive and memory CD4 T cells is abrogated in the presence of T cell-activating cytokines., Methods: CD4 T cell subsets (naive [Tn], central memory [Tcm], and effector memory [Tem] T cells) were isolated from the peripheral blood (PB) of healthy controls and the PB and synovial fluid (SF) of rheumatoid arthritis (RA) patients. CD4 T cells were cocultured with autologous, thymic stromal lymphopoietin (TSLP)-primed CD1c MDCs in the presence or absence of abatacept (CTLA-4Ig) and/or interleukin-7 (IL-7) or IL-15. Subsequently, T cell proliferation and cytokine production were measured., Results: The percentages of each CD4 T cell subset from the circulation of healthy controls and RA patients were comparable and mainly consisted of Tn and Tcm cells, whereas the SF of RA patients mainly consisted of Tcm and Tem cells. Activation of CD4 T cell subsets by TSLP-primed MDCs from the RA PB was completely blocked by abatacept. Addition of IL-7 or IL-15 to the cocultures strongly increased CD4 T cell activation and overruled the inhibitory capacity of abatacept. IL-7-induced reversal was associated with robust induction of interferon-γ, tumor necrosis factor α, and IL-17 secretion. Similarly, CD4 T cell proliferation induced by TSLP-primed MDCs from the SF of RA patients was strongly blocked by abatacept, but this inhibitory effect was vigorously overruled in the presence of IL-7., Conclusion: These findings indicate that the presence of T cell-activating cytokines such as IL-7 or IL-15 in the joints of RA patients reduces the capacity of abatacept to inhibit MDC-driven CD4 T cell activation. This mechanism may be one explanation for the partial, and sometimes absent, response to abatacept therapy in a subset of patients., (Copyright © 2015 by the American College of Rheumatology.)
- Published
- 2015
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6. Thymic stromal lymphopoietin, a novel proinflammatory mediator in rheumatoid arthritis that potently activates CD1c+ myeloid dendritic cells to attract and stimulate T cells.
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Moret FM, Hack CE, van der Wurff-Jacobs KM, Radstake TR, Lafeber FP, and van Roon JA
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- Adult, Aged, Arthritis, Rheumatoid physiopathology, Cell Count, Cell Proliferation, Cells, Cultured, Chemotaxis physiology, Cytokines pharmacology, Dendritic Cells drug effects, Dendritic Cells metabolism, Female, Humans, Inflammation physiopathology, Male, Middle Aged, Myeloid Cells drug effects, Myeloid Cells metabolism, Osteoarthritis metabolism, Osteoarthritis physiopathology, Receptors, Cytokine metabolism, Synovial Fluid metabolism, Thymic Stromal Lymphopoietin, Antigens, CD1 metabolism, Arthritis, Rheumatoid metabolism, CD4-Positive T-Lymphocytes pathology, Cell Communication physiology, Cytokines metabolism, Dendritic Cells pathology, Glycoproteins metabolism, Inflammation metabolism, Myeloid Cells pathology
- Abstract
Objective: To determine the levels of thymic stromal lymphopoietin (TSLP) and the numbers of TSLP receptor (TSLPR)-expressing CD1c+ (blood dendritic cell antigen 1-positive) myeloid dendritic cells (MDCs) in the joints as compared with the peripheral blood (PB) of patients with rheumatoid arthritis (RA), as well as to determine the capacity of TSLP to induce MDC-dependent T cell activation., Methods: TSLP levels were measured in synovial fluid (SF) samples from patients with RA and those with osteoarthritis (OA). MDC numbers in PB and SF samples from RA patients and TSLPR expression on these cells were assessed by fluorescence-activated cell sorter analysis. PB and SF MDCs from RA patients were stimulated with TSLP, and cytokine production was measured by multiplex immunoassay. TSLP-primed MDCs were cocultured with autologous CD4+ T cells in the absence of additional stimuli, and subsequently, cell proliferation and cytokine production were measured., Results: TSLP levels were significantly increased in SF samples from RA versus OA patients. The numbers of TSLPR-expressing MDCs in the SF of RA patients were significantly increased as compared to those in the PB, and SF MDCs displayed increased levels of TSLPR. TSLP selectively stimulated the production of thymus and activation-regulated chemokine and macrophage inflammatory protein 1α by CD1c+ MDCs. TSLP-primed MDCs from PB and SF potently stimulated the proliferation of autologous CD4+ T cells as compared to unstimulated MDCs. Enhanced proliferation was associated with increased production of interferon-γ, interleukin-17 (IL-17), and IL-4., Conclusion: These data support an inflammatory mechanism by which increased intraarticular TSLP in RA potently activates TSLPR-expressing CD1c+ MDCs in the joints to secrete chemokines, causing chemotaxis and subsequent activation of CD4+ T cells. In addition to the demonstrated inflammatory potential of TSLP in experimental arthritis, this suggests that TSLP and TSLPR-expressing MDCs could both play a pivotal role in the immunopathology of RA., (Copyright © 2014 by the American College of Rheumatology.)
- Published
- 2014
- Full Text
- View/download PDF
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