Expression of interleukin‐21 receptor, but not interleukin‐21, in synovial fibroblasts and synovial macrophages of patients with rheumatoid arthritis

Jüngel, Astrid; Distler, Jörg H W; Kurowska‐Stolarska, Mariola; Seemayer, Christian A.; Seibl, Reinhart; Forster, Adrian; Michel, Beat A.; Emmrich, Frank; Distler, Oliver

doi:10.1002/art.20218

Cited by 162 publications

(153 citation statements)

References 16 publications

(25 reference statements)

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“…Therefore, we used an ELISA to measure IL-21 production in cultured FLS. However, similar to what was observed in a previous study (22), IL-21 was not expressed by cultured RA FLS (data not shown). We also examined serum IL-21 concentrations, which were shown to be significantly higher in patients with RA (n ϭ 30) than in patients with OA (n ϭ 29) (mean Ϯ SD 332.1 Ϯ 121 pg/ml and 131.5 Ϯ 56 pg/ml, respectively; P Ͻ 0.01).…”

supporting

confidence: 91%

Interleukin‐21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen‐induced arthritis

Kwok

Cho

Park

et al. 2012

Arthritis & Rheumatism

104

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Objective. Bone destruction is a critical pathology involved in the functional disability caused by rheumatoid arthritis (RA). Osteoclasts, which are specialized bone-resorbing cells regulated by cytokines such as RANKL, are implicated in bone destruction in RA. The aim of this study was to determine whether interleukin-21 (IL-21), a potent immunomodulatory 4-␣-helical bundle type 1 cytokine, has osteoclastogenic activity in patients with RA and in mice with collageninduced arthritis (CIA).Methods. The expression of IL-21 in synovial tissue was examined using immunohistochemistry. The concentrations of IL-21 in serum and synovial fluid were determined by enzyme-linked immunosorbent assay.

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supporting

confidence: 91%

Interleukin‐21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen‐induced arthritis

Kwok

Cho

Park

et al. 2012

Arthritis & Rheumatism

104

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“…Indeed, we recently showed that IL-21 is produced in excess in the inflamed gut of patients with inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, and that IL-21 helps sustain the ongoing Th1 cell response in the gut of patients with Crohn's disease (3). Moreover, enhanced expression of IL-21 and IL-21R has been described in patients with systemic sclerosis (4), and up-regulation of IL-21R also occurs in synovial macrophages and fibroblasts of patients with rheumatoid arthritis (24). Studies in experimental models of autoimmune diseases have also shown that administration of IL-21 into mice enhances the recruitment of leukocytes into inflamed tissues and increases the severity of the inflammation (25).…”

Section: Discussionmentioning

confidence: 99%

IL-21 Counteracts the Regulatory T Cell-Mediated Suppression of Human CD4+ T Lymphocytes

Peluso

Fantini

Fina

et al. 2007

The Journal of Immunology

266

208

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High expression of IL-21 and/or IL-21R has been described in T cell-mediated inflammatory diseases characterized by defects of counterregulatory mechanisms. CD4+CD25+ regulatory T cells (Treg) are a T cell subset involved in the control of the immune responses. A diminished ability of these cells to inhibit T cell activation has been documented in immune-inflammatory diseases, raising the possibility that inflammatory stimuli can block the regulatory properties of Treg. We therefore examined whether IL-21 controls CD4+CD25+ T cell function. We demonstrate in this study that IL-21 markedly enhances the proliferation of human CD4+CD25− T cells and counteracts the suppressive activities of CD4+CD25+ T cells on CD4+CD25− T cells without affecting the percentage of Foxp3+ cells or survival of Treg. Additionally, CD4+CD25+ T cells induced in the presence of IL-21 maintain the ability to suppress alloresponses. Notably, IL-21 enhances the growth of CD8+CD25− T cells but does not revert the CD4+CD25+ T cell-mediated suppression of this cell type, indicating that IL-21 makes CD4+ T cells resistant to suppression rather than inhibiting CD4+CD25+ T cell activity. Finally, we show that IL-2, IL-7, and IL-15, but not IL-21, reverse the anergic phenotype of CD4+CD25+ T cells. Data indicate that IL-21 renders human CD4+CD25− T cells resistant to Treg-mediated suppression and suggest a novel mechanism by which IL-21 could augment T cell-activated responses in human immune-inflammatory diseases.

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“…Limitations of in vitro migration assays include evaluating the role of a particular chemokine as it relates to other chemokines and chemokine receptors, and ranking the importance of chemokines and chemokine receptors in a particular disease. Indeed, many investigators have used a similar SCID mouse chimera to study the effects of gene therapy and RA ST fibroblast infiltration in vivo (41)(42)(43). Therefore, to evaluate the proinflammatory function of chemokines in RA, we developed an in vivo cell migration assay to determine the relative importance of chemokines and their respective cellular receptors in a human RA ST-SCID mouse chimera.…”

Section: Discussionmentioning

confidence: 99%

CXCL16‐mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway

Ruth¹,

Haas²,

Park³

et al. 2006

Arthritis & Rheumatism

107

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Objective. Rheumatoid arthritis (RA) is characterized by profound mononuclear cell (MNC) recruitment into synovial tissue (ST), thought to be due in part to tumor necrosis factor ␣ (TNF␣), a therapeutic target for RA. Although chemokines may also be involved, the mechanisms remain unclear. We undertook this study to examine the participation of CXCL16, a novel chemokine, in recruitment of MNCs to RA ST in vivo and to determine the signal transduction pathways mediating this process. Conclusion. Taken together, these results point to a unique role for CXCL16 as a premier MNC recruiter in RA and suggest additional therapeutic possibilities, targeting CXCL16, its receptor, or its signaling pathways.

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Expression of interleukin‐21 receptor, but not interleukin‐21, in synovial fibroblasts and synovial macrophages of patients with rheumatoid arthritis

Cited by 162 publications

References 16 publications

Interleukin‐21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen‐induced arthritis

Interleukin‐21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen‐induced arthritis

IL-21 Counteracts the Regulatory T Cell-Mediated Suppression of Human CD4+ T Lymphocytes

CXCL16‐mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway

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