The role and modulation of CCR6+ Th17 cell populations in rheumatoid arthritis

Paulissen, Sandra M. J.; Hamburg, Jan Piet van; Dankers, Wendy; Lubberts, Erik

doi:10.1016/j.cyto.2015.02.002

Cited by 121 publications

(112 citation statements)

References 146 publications

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“…Classic Th1 cells that express the lineage-associated transcription factor TBX21 and produce high levels of IFN-g are CCR4 2 CCR6 2 CXCR3 + , whereas classic Th2 cells, which express GATA3 and mainly produce IL-4 and IL-5, are CCR4 + CCR6 2 CXCR3 2 [7][8][9]. Th17 cells that express RORC and produce IL-17A mainly reside within the CCR6 + T cell population and are also positive for CCR4 but negative for CXCR3 [8,10].…”

Section: Introductionmentioning

confidence: 97%

“…However, nonclassic Th1 cells also reside within the CCR6 + T cell population but do not express CCR4. These cells, also referred to as Th1/Th17 or Th17.1 cells, display both Th1 and Th17 characteristics, in that they express both TBX21 and RORC and produce IFN-g and IL-17A [8,9,11].…”

Section: Introductionmentioning

confidence: 99%

“…The purpose of this study was to perform a comprehensive analysis of the CD4 + T cell subtype profile in blood from patients with ueRA compared with that of HCs, by using a well-defined flow cytometry gating strategy for classic Th1, Th2, and Th17 subsets and for Th1/Th17, Tfh, and Treg cells [7][8][9][10][11]. For the first time, we also characterized the fraction of CXCR3 + cells within the CCR4 + CCR6 + subset (herein denoted CXCR3 + Th17), the CXCR3 + fraction within the CCR4 + CCR6 2 subset (denoted CXCR3 + Th2), and the fraction of cells that expressed only CCR6 (denoted CCR6 + only) and compared the proportions of these cells among patients with ueRA and HC subjects.…”

Section: Introductionmentioning

confidence: 99%

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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: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Studies have also shown that the pathogenic signature is not confined to cells producing high levels of IL-17A, but that even CCR6 + Th cell populations producing low amounts of IL-17A display a pathogenic signature and activity. 27 Therefore, the cell populations producing IL-17 can form an important target for RA therapy.…”

mentioning

confidence: 99%

Molecular targets in arthritis and recent trends in nanotherapy

Roy¹,

Kanwar²,

Kanwar³

2015

IJN

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Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy.

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“…Lubberts and colleagues [53] discussed the role of CCR6+ Th cells in the pathogenesis of RA, including the progression of early inflammation to persistent arthritis. They also highlighted the phenotypic and functional heterogeneity as well as the plasticity of CCR6+ Th cells, and described various therapeutic approaches under development that are based on this T cell subset.…”

Section: Introductionmentioning

confidence: 98%

Interplay among cytokines and T cell subsets in the progression and control of immune-mediated diseases

Moudgil

2015

Cytokine

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The role and modulation of CCR6+ Th17 cell populations in rheumatoid arthritis

Cited by 121 publications

References 146 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

Molecular targets in arthritis and recent trends in nanotherapy

Interplay among cytokines and T cell subsets in the progression and control of immune-mediated diseases

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The role and modulation of CCR6+ Th17 cell populations in rheumatoid arthritis

Cited by 121 publications

References 146 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

Molecular targets in arthritis and recent trends in&nbsp;nanotherapy

Interplay among cytokines and T cell subsets in the progression and control of immune-mediated diseases

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Product

Resources

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Molecular targets in arthritis and recent trends in nanotherapy