IL-17/Th17 mediated synovial inflammation is IL-22 independent

Hamburg, Jan Piet van; Corneth, Odilia B. J.; Paulissen, Sandra M. J.; Davelaar, Nadine; Asmawidjaja, Patrick S.; Mus, Anne‐Marie; Lubberts, Erik

doi:10.1136/annrheumdis-2012-202373

Cited by 66 publications

(49 citation statements)

References 46 publications

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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].…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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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“…Cowan et al [85] found that both the Th17 response and IL-22 were differentially induced and observed a correlation between down regulation of IL-22 and progression of infection. These results correlate with those of van Hamburg et al [122], who investigated the effects of the Th17 response on IL-22 in rheumatoid arthritis. As with Cowan et al [85], the levels of IL-22 were negatively correlated with the progression of disease; an interaction primarily mediated by Th17.…”

Section: Modulation Of the Immune Responsesupporting

confidence: 90%

Vaccines against Mycobacterium Tuberculosis: Exploring Alternate Strategies to Combat a Near-perfect Pathogen

Filion¹,

Al‐Ahdal²,

Tetro³

2013

Mycobact Dis

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“…Number of Th17 cells is increased in peripheral blood of RA patients, and IL-17, which is greatly released in plasma and synovial fluid, has relevant roles mediating inflammation, microvascular function, and atherosclerosis. [37][38][39] On the contrary, although IL-17 levels strongly correlated with anti-CCP levels, in vitro treatment of normal lymphocytes with antiCCPs did not induce its expression. In this regard, it has been demonstrated that monocytes and fibroblasts from inflamed joints are able to induce the development of Th17 cells, 40,41 suggesting that interactions with other activated cells might be further required to induce the expression of IL17.…”

Section: Discussionmentioning

confidence: 88%

Anticyclic Citrullinated Protein Antibodies Are Implicated in the Development of Cardiovascular Disease in Rheumatoid Arthritis

Barbarroja

Pérez-Sánchez

Ruiz-Limón

et al. 2014

ATVB

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Objective— Previous studies have suggested a relationship between anticyclic citrullinated protein (CCP) levels and development of cardiovascular disease in rheumatoid arthritis (RA). However, a limited number of studies have demonstrated an involvement of anti-CCPs in those processes. This study was aimed to define the specific role of these auto-antibodies in the pro-oxidative, inflammatory, and proatherogenic profile observed in leukocytes from RA patients. Approach and Results— Seventy-five RA patients and 31 healthy donors were enrolled. Carotid intima media thickness was evaluated as atherosclerosis marker. Several procoagulant and inflammatory factors, leukocyte activation, and oxidative stress markers were analyzed in plasma and leukocyte subsets. Anti-CCPs were purified from plasma of RA patients, and in vitro treatment of healthy leukocytes was conducted. High titers of anti-CCPs were associated to altered expression of prothrombotic and inflammatory markers, high oxidative stress, and pathological carotid intima media thickness in RA patients. Notably, gene expression analysis showed that lymphocytes were major players in altered inflammatory profile, monocytes were responsible for the protrombotic and atherogenic status, and neutrophils mainly displayed a pro-oxidative feature. In vitro treatment with purified anti-CCPs fully recapitulated that pathogenic profile, promoting the activation of leukocytes. Conclusions— Anti-CCPs are key players in the inflammatory and proatherogenic status of RA patients. The effects are specific of the immune cell targeted, promoting overexpression of thrombotic, inflammatory, and pro-oxidative markers in monocytes; pro-oxidative status in neutrophils; and proinflammatory profile in lymphocytes. Targeting these autoantibodies would be an excellent strategy to prevent the development of cardiovascular disease in RA.

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IL-17/Th17 mediated synovial inflammation is IL-22 independent

Abstract: These findings show that IL-17A/Th17 cell-mediated synovial inflammation is independent of IL-22 and Th22 cells. This implies that targeting IL-17A/Th17 cells, rather than IL-22/Th22 cells, should be the focus for treatment of T cell-mediated synovial inflammation.

Cited by 66 publications

References 46 publications

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

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

Vaccines against Mycobacterium Tuberculosis: Exploring Alternate Strategies to Combat a Near-perfect Pathogen

Anticyclic Citrullinated Protein Antibodies Are Implicated in the Development of Cardiovascular Disease in Rheumatoid Arthritis

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