Potential role of Th17 cells in the pathogenesis of adult-onset Still's disease

Chen, Der‐Yuan; Chen, Yiming; Lan, Joung‐Liang; Lin, Chi-Chen; Chen, Hsin‐Hua; Hsieh, Chia‐Wei

doi:10.1093/rheumatology/keq284

Cited by 81 publications

(59 citation statements)

References 38 publications

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“…In order to detect circulating Th17 cells, phycoerythrin (PE)-conjugated anti-IL-17 (eBioscience, San Diego, CA, USA) and Phycoerythrin-Cyanin 5 (PC5)-conjugated anti-CD4 (Beckman Coulter, Marseilles, France) were quantified using flow cytometry according to the manufacturer's protocol and a technique previously described [34,35]. Briefly, aliquots of 1,000 μl of the sterile heparinized whole blood were stimulated with a combination of 25 ng/ml of phorbol myristate acetate and 1 μg/ml of ionomycin (Sigma, Deisenhofen, Germany) and cultured for one hour at 37°C in a humidified 5% CO 2 incubator.…”

Section: Methodsmentioning

confidence: 99%

Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy

et al. 2011

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IntroductionThe objective of this study was to investigate the effects of tumor necrosis factor (TNF)-α inhibitors on circulating T helper-type 17 (Th17) cells and Th17-related cytokines in patients with rheumatoid arthritis (RA).MethodsThe frequencies of circulating Th17 cells and serum levels of Th17-related cytokines were determined using flow cytometry analysis and ELISA, respectively, in 48 RA patients both before (baseline) and six months after anti-TNF-α therapy. Therapeutic response was evaluated using European League Against Rheumatism (EULAR) response criteria.ResultsSignificantly higher baseline frequencies of circulating Th17 cells and serum levels of interleukin (IL)-6, IL-17, IL-21, IL-23 and TNF-α were observed in active RA patients than in 12 healthy controls (all P < 0.001). After anti-TNF-α therapy, 36 patients (75%) were EULAR responders (20 good responders and 16 moderate responders) and 12 (25.0%) were non-responders. The mean levels of circulating Th17 cells and IL-17 significantly decreased (1.13% vs. 0.79%; 43.1 pg/ml vs. 27.8 pg/ml; respectively, both P < 0.001) in parallel with clinical remission in responders. Levels of IL-6, IL-21, IL-23 and TNF-α were significantly decreased after anti-TNF-α therapy in responders. In contrast, the mean levels of circulating Th17 cells and IL-17 significantly increased after anti-TNF-α therapy (2.94% vs. 4.23%; 92.1 pg/ml vs. 148.6 pg/ml; respectively, both P < 0.05) in non-responders. Logistic regression analysis identified a high baseline level of IL-17 as a significant predictor of poor therapeutic response.ConclusionsThe beneficial effect of anti-TNF-α therapy might involve a decrease in Th17-related cytokines in responders, whereas rising levels of circulating Th17-cells and IL-17 were observed in patients with an inadequate response to anti-TNF-α therapy.

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Section: Methodsmentioning

confidence: 99%

Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy

et al. 2011

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“…The TLR7-MyD88 pathway, leading to neutrophil recruitment and Th17 response, is also activated in the dendritic cells of AOSD patients [41,42]. TLR4 is involved in sJIA pathophysiology through the recognition of S100 calcium-binding proteins [43].…”

Section: Geneticsmentioning

confidence: 99%

“…The differentiation of naïve T cells into Th17 cells, producing IL-17, is supported by several cytokines including IL-18, IL-1b, IL-6, and IL-23. Recently, Chen et al [42] have shown that circulating Th17 cells are significantly higher in patients with active untreated AOSD than in healthy controls. The levels of Th17 cells correlated with disease activity, ferritin, and response to treatment.…”

Section: Cytokinesmentioning

confidence: 99%

Pathogenesis of adult-onset Still’s disease: new insights from the juvenile counterpart

et al. 2014

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Adult-onset Still's disease (AOSD) is a rare inflammatory disease characterized by the classical triad of daily fever, arthritis, and typical salmon-colored rash. Recent accumulation of knowledge, mostly arising from hereditary autoinflammatory diseases and from the systemic-onset juvenile idiopathic arthritis (sJIA), has given raise to new hypotheses on the pathophysiology of AOSD. In this review, we first discuss on the continuum between AOSD and sJIA. Then, we summarize current hypotheses on the underlying pathogenesis: (1) an infectious hypothesis; (2) an autoinflammatory hypothesis; (3) a lymphohistiocytic hypothesis; and (4) a hyperferritinemic hypothesis. Finally, we present the recent data suggesting that patients with AOSD fall into two distinct subgroups with different courses, one with prominent systemic features and one with chronic arthritis.

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“…In this study, it was found that Th17 cells are significantly elevated in patients with active untreated AOSD compared to healthy volunteers. Further, the cells decrease nearly 10-fold during clinical remission and serum levels of ferritin decrease as well [97]. The frequencies of Th17 cells are similarly elevated in patients with active SLE, which was previously shown to have increased Th17 cells [98].…”

Section: Adult Onset Still's Disorder and Th17mentioning

confidence: 99%

Th17 Response and Inflammatory Autoimmune Diseases

Waite

Skokos

2012

International Journal of Inflammation

193

149

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The proinflammatory activity of T helper 17 (Th17) cells can be beneficial to the host during infection. However, uncontrolled or inappropriate Th17 activation has been linked to several autoimmune and autoinflammatory pathologies. Indeed, preclinical and clinical data show that Th17 cells are associated with several autoimmune diseases such as arthritis, multiple sclerosis, psoriasis, and lupus. Furthermore, targeting the interleukin-17 (IL-17) pathway has attenuated disease severity in preclinical models of autoimmune diseases. Interestingly, a recent report brings to light a potential role for Th17 cells in the autoinflammatory disorder adult-onset Still's disease (AOSD). Whether Th17 cells are the cause or are directly involved in AOSD remains to be shown. In this paper, we discuss the biology of Th17 cells, their role in autoimmune disease development, and in AOSD in particular, as well as the growing interest of the pharmaceutical industry in their use as therapeutic targets.

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Potential role of Th17 cells in the pathogenesis of adult-onset Still's disease

Cited by 81 publications

References 38 publications

Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy

Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy

Pathogenesis of adult-onset Still’s disease: new insights from the juvenile counterpart

Th17 Response and Inflammatory Autoimmune Diseases

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