Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127^low Treg Cells in Patients with Chronic Rheumatoid Arthritis

OBJECTIVE: Conflicting evidence exists regarding the suppressive capacity of Treg cells in the peripheral blood (PB) of patients with rheumatoid arthritis (RA). The aim of this study was to determine whether Treg cells are intrinsically defective in RA. METHODS: Using a range of assays on PB samples from patients with chronic RA and healthy controls, CD3+CD4+CD25+CD127(low) Treg cells from the CD45RO+ or CD45RA+ T cell compartments were analyzed for phenotype, cytokine expression (ex vivo and after in vitro stimulation), suppression of Teff cell proliferation and cytokine production, suppression of monocyte-derived cytokine/chemokine production, and gene expression profiles. RESULTS: No differences between RA patients and healthy controls were observed with regard to the frequency of Treg cells, ex vivo phenotype (CD4, CD25, CD127, CD39, or CD161), or proinflammatory cytokine profile (interleukin-17 [IL-17], interferon-γ [IFNγ], or tumor necrosis factor [TNF]). FoxP3 expression was slightly increased in Treg cells from RA patients. The ability of Treg cells to suppress the proliferation of T cells or the production of cytokines (IFNγ or TNF) upon coculture with autologous CD45RO+ Teff cells and monocytes was not significantly different between RA patients and healthy controls. In PB samples from some RA patients, CD45RO+ Treg cells showed an impaired ability to suppress the production of certain cytokines/chemokines (IL-1β, IL-1 receptor antagonist, IL-7, CCL3, or CCL4) by autologous lipopolysaccharide-activated monocytes. However, this was not observed in all patients, and other cytokines/chemokines (TNF, IL-6, IL-8, IL-12, IL-15, or CCL5) were generally suppressed. Finally, gene expression profiling of CD45RA+ or CD45RO+ Treg cells from the PB revealed no statistically significant differences between RA patients and healthy controls. CONCLUSION: Our findings indicate that there is no global defect in either CD45RO+ or CD45RA+ Treg cells in the PB of patients with chronic RA

Orale manifestaties van systemische sclerose

Systemische sclerose is een relatief zeldzame bindweefselziekte, waarbij door een verhoogde afzetting van collageen vaak ernstige en progressieve fibrose van de huid ontstaat, en soms ook van de interne organen. Aantasting van de speekselklieren veroorzaakt hyposialie en xerostomie. Verstrakking van de huid verkleint de mondopening, waardoor de mondhygiëne en het verrichten van tandheelkundige ingrepen worden bemoeilijkt. Parodontitis en resorptie van kaakbot worden bij patiënten met systemische sclerose frequenter gerapporteerd

Novel insights in the pathogenesis of systemic sclerosis

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