Interleukin‐17–producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers

Nistala, Kiran; Moncrieffe, Halima; Newton, Katy; Varsani, H; Hunter, Patricia J.; Wedderburn, Lucy R.

doi:10.1002/art.23291

Cited by 296 publications

(265 citation statements)

References 51 publications

(62 reference statements)

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“…Therefore, it is very conceivable that the low levels of IL-17 detected in the present study are biologically relevant in an inflamed milieu. The frequencies of Th17 cells reported herein are also consistent with the frequencies of IL-17-positive cells reported by others (18,19,34,35). The tight association of Th17 cell frequencies with RA disease activity at the onset of disease ( Figure 1) and in established RA (Figure 3) clearly points toward a role for this T cell subset in the pathophysiology of the disease.…”

Section: Discussionsupporting

confidence: 90%

Role of Th17 cells in human autoimmune arthritis

Leipe¹,

Grünke²,

Dechant³

et al. 2010

Arthritis & Rheumatism

384

330

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Objective. To delineate the role of Th17 cells in the pathogenesis of autoimmune arthritides.Methods. Th17 cells were analyzed in well-defined homogeneous cohorts of patients with the prototypical autoimmune arthritides rheumatoid arthritis (RA) and psoriatic arthritis (PsA), grouped according to patients who had very early active RA (n ‫؍‬ 36; mean disease duration 2.8 months, Disease Activity Score in 28 joints 5.0) and those who had very early active PsA (n ‫؍‬ 20; mean disease duration 2.3 months), none of whom had received treatment with glucocorticoids or diseasemodifying antirheumatic drugs, as well as patients with established RA (n ‫؍‬ 21; mean disease duration 68 months) who were considered either responders or nonresponders to therapy. Groups of healthy individuals and patients with osteoarthritis (a noninflammatory arthritis) were used as control cohorts. Expression of T lineage-specific transcription factors (RORC, T-bet, GATA-3, and FoxP3) and the response of CD4 T cells to Th17 cell-inducing conditions were analyzed in vitro.Results. The frequencies of Th17 cells and levels of interleukin-17 strongly correlated with systemic disease activity at both the onset and the progression of RA or PsA. The values were reduced to control levels in patients with treatment-controlled disease activity.Th17 cells were enriched in the joints, and increased frequencies of synovial Th17 cells expressed CCR4 and CCR6, indicative of selective migration of Th17 cells to the joints. The intrinsically elevated expression of RORC, accompanied by biased Th17 cell development, and the resistance of Th17 cells to a natural cytokine antagonist in patients with RA and patients with PsA were suggestive of the underlying molecular mechanisms of uncontrolled Th17 activity in these patients.Conclusion. Th17 cells play an important role in inflammation in human autoimmune arthritides, both at the onset and in established disease.

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Section: Discussionsupporting

confidence: 90%

Role of Th17 cells in human autoimmune arthritis

Leipe¹,

Grünke²,

Dechant³

et al. 2010

Arthritis & Rheumatism

384

330

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“…IL-17 may also contribute directly to joint damage, because it was shown to act synergistically with TNF-␣ and/or IL-1␤ to induce cartilage destruction in vitro and in experimental arthritis in vivo (17)(18)(19). In RA, SM IL-17 expression in synergy with TNF-␣ is predictive of joint damage progression (20), and, in juvenile idiopathic arthritis (JIA), the number of IL-17-expressing T cells is higher in patients with the more severe form of disease (21). Despite these data, very little is known about what drives human Th17 responses in vivo, particularly at sites of inflammation.…”

Section: Discussionmentioning

confidence: 99%

In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses

Evans

Gullick

Kelly

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

170

163

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“…[107][108][109][110] Considering the central role of Th17 cells in autoimmune diseases including rheumatoid arthritis (RA) and psoriasis, mutations in inflammasome-encoding genes may result in a broad spectrum of Th17 cell-mediated autoimmune disorders, through deregulation of IL-1b secretion. 107,[111][112][113][114][115][116] Genetic variants in several inflammatory genes, including NLRP3, are associated with two forms of autoimmune arthritis: juvenile idiopathic arthritis and RA, characterized by Th17 cells. 117,118 Indeed, increased expression of NLRP3 was observed in the synovium of RA patients compared to subjects suffering from non-autoimmune osteoarthritis.…”

Section: Adaptive Immunity-mediated Diseasesmentioning

confidence: 99%

The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond

2011

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Nucleotide-binding oligomerization domain (NOD)-containing protein-like receptors (NLRs) are a recently discovered class of innate immune receptors that play a crucial role in initiating the inflammatory response following pathogen recognition. Some NLRs form the framework for cytosolic platforms called inflammasomes, which orchestrate the early inflammatory process via IL-1b activation. Mutations and polymorphisms in NLR-coding genes or in genetic loci encoding inflammasome-related proteins correlate with a variety of autoinflammatory diseases. Moreover, the activity of certain inflammasomes is associated with susceptibility to infections as well as autoimmunity and tumorigenesis. In this review, we will discuss how identifying the genetic characteristics of inflammasomes is assisting our understanding of both autoinflammatory diseases as well as other immune system-driven disorders.

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Interleukin‐17–producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers

Cited by 296 publications

References 51 publications

Role of Th17 cells in human autoimmune arthritis

Role of Th17 cells in human autoimmune arthritis

In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses

The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond

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