Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

Cascão, Rita; Moura, Rita A; Perpétuo, I.P.; Canhão, Helena; Sousa, E; Mourão, Ana Filipa; Polido-Pereira, Joaquim; Queiróz, M Viana; Rosário, H S; Souto-Carneiro, Margarida; Graça, Luís

doi:10.1186/1479-5876-8-s1-p34

Cited by 18 publications

(24 citation statements)

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“…Take a look into our RA patients' samples, we find a significant elevation in most of cytokines that we have measured such as IL-6, IL-17, IL-23, IL-4 and TGF-b1. Our data are consistent with previously reported data [46][47][48] that have stressed on the potential predominant role of TH17 cells in the inflammatory process and chronic progression in RA which coincides with a reduction in frequencies of Treg cells in peripheral blood of RA patients. Sivalingam et al [47] reported that the pro-inflammatory cytokines (such as IL-6) were significantly elevated in RA patients.…”

Section: Discussionsupporting

confidence: 95%

“…RA has been observed to be associated with high levels of IL-6 in the synovial membrane and plasma in data of several studies [49,50]. Cascão et al [46] found a high plasma concentration of IL-17A in RA patients. It has been reported that IL-6 and IL-17 are elevated in the plasma and this correlates with a higher disease activity [46,51].…”

Section: Discussionmentioning

confidence: 96%

“…Cascão et al [46] found a high plasma concentration of IL-17A in RA patients. It has been reported that IL-6 and IL-17 are elevated in the plasma and this correlates with a higher disease activity [46,51].…”

Section: Discussionmentioning

confidence: 98%

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Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity

et al. 2015

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Section: Discussionsupporting

confidence: 95%

Section: Discussionmentioning

confidence: 96%

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Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity

et al. 2015

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“…Nevertheless, an increased frequency of circulating Th17 cells has been reported in early RA, where Th17 cells were defined based on chemokine receptors [33]. Also, in line with our results, patients with very early RA have had increased serum levels of the Th17 polarizing cytokines IL-1b and -6 and of the Th17-derived cytokines IL-17A, IL-22, and IL-8 [34]. The role of Th17 cells in RA pathogenesis is well established.…”

Section: Discussionsupporting

confidence: 91%

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

Pandya

Lundell

Hallström

et al. 2016

Journal of Leukocyte Biology

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The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral blood mononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age- and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25 CD127 and also FOXP3 CXCR5 cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4CXCR3 (Th2 and Th17), CTLA4 and FOXP3 subsets were present in significantly higher frequencies, whereas CCR4 (Th1/Th17, CCR6CCR4CXCR3, and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3/interferon γ-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4CXCR3 T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of these cells in early stages of the disease.

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“…More recently, Cascão et al [37] have reported increased serum levels of the Th17-promoting IL1 and IL6 as well as IL8 and Th17 characteristic IL17A and IL22 in patients with very early RA. In those with established RA, however, this pattern of cytokine dysregulation was more evident within the synovial Xuid.…”

Section: Inxammatory Arthritis and Disturbed T Cell Functionmentioning

confidence: 97%

T helper cell subsets in arthritis and the benefits of immunomodulation by 1,25(OH)2 vitamin D

et al. 2011

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The prevalence of vitamin D deficiency has been shown to be increased in many of the common arthritides. Importantly, vitamin D has significant immunomodulatory effects in addition to its role in calcium homoeostasis. Both aspects of its function have a major bearing on joint disease whether as part of an inflammatory arthritis or from wear and tear. While the exact mechanisms still require clarification, there is now compelling evidence that the hormonally active 1,25-dihydroxycholecalciferol vitamin D can reduce the activity of the proinflammatory Th1 and Th17 T cell subsets. Additionally, it is stimulatory of enhanced anti-inflammatory Th2 activity at the same time as promoting T regulatory cell activity. These various actions suggest that correcting vitamin D deficiency should be a important part of the management of all patients with joint disease. For the future, vitamin D analogues with enhanced immunomodulatory properties but with reduced ability to increase calcium are being investigated.

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Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

Cited by 18 publications

References 0 publications

Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity

Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

T helper cell subsets in arthritis and the benefits of immunomodulation by 1,25(OH)2 vitamin D

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