Induction of cartilage damage by overexpression of T cell interleukin‐17A in experimental arthritis in mice deficient in interleukin‐1

Koenders, Marije I.; Lubberts, Erik; Oppers‐Walgreen, Birgitte; Bersselaar, Liduine van den; Helsen, Monique M.; Kolls, Jay K.; Joosten, Leo A. B.; Berg, Wim B. van den

doi:10.1002/art.20885

Cited by 90 publications

(75 citation statements)

References 42 publications

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“…IL-17 is highly pathogenic to cartilage and bone in various T cell-mediated experimental models of arthritis, including SCW arthritis, and has been shown to be able to take over the catabolic functions of IL-1 (32,34). Importantly, recent evidence indicates that conditioned medium from TLR-4-activated dendritic cells is sufficient to induce Th17 differentiation when TGF␤ is added (47).…”

Section: Discussionmentioning

confidence: 99%

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Shift from toll‐like receptor 2 (TLR‐2) toward TLR‐4 dependency in the erosive stage of chronic streptococcal cell wall arthritis coincident with TLR‐4–mediated interleukin‐17 production

Abdollahi‐Roodsaz¹,

Joosten²,

Helsen³

et al. 2008

Arthritis & Rheumatism

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Section: Discussionmentioning

confidence: 99%

“…Irreversible proteoglycan damage by MMP activity in cartilage was assessed by immunostaining for the neoepitope VDIPEN, as described previously (34).…”

Section: Methodsmentioning

confidence: 99%

Shift from toll‐like receptor 2 (TLR‐2) toward TLR‐4 dependency in the erosive stage of chronic streptococcal cell wall arthritis coincident with TLR‐4–mediated interleukin‐17 production

Abdollahi‐Roodsaz¹,

Joosten²,

Helsen³

et al. 2008

Arthritis & Rheumatism

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“…Enhances IL-1 mediated IL-6 in RA synoviocytes as well as TNF-induced synthesis of IL-1, IL-6, IL-8 [15,16] IL-17 additative/synergistic effect with TNF or IL-1 [33] IL-17 synergize with IL-1, TNF [10,20,32] IL-17 effect is TNF dependent under naïve conditions, but TNF independent under arthritis conditions [38] IL-17 effect is IL-1 independent in experimental arthritis [8,37] IL-17 in bone damage IL-17 induces RANKL in cultures of osteoblasts [13] IL-17 induces bone damage in naïve mice, aggravates bone erosion in CIA [44] Synergy between IL-17 and TNF [20,25,32] IL-17-induced bone erosion is RANKL mediated [44] IL-17 in cartilage damage IL-17 induces NO [34], metalloproteinases in synoviocytes and chondrocytes [17][18][19] Inducer of NO and MMPs and inhibition of PG synthesis [26], aggravates cartilage erosion in CIA [8,9] Synergy between IL-17 and TNF [29] IL-1 independent role of IL-17 in cartilage damage [8,19,28] Th17 IL-17-producing cells in the synovium of RA patients (Th0/Th1 but not Th2) [14] IL-17-producing cells and Th17 in CIA and AIA arthritis models [55,60,70] effects of IL-17 on matrix degradation and synthesis were not dependent on IL-1 production by chondrocytes and IL-1Ra did not block IL-17-induced matrix release nor prevented inhibition of matrix synthesis in vitro using porcine articular cartilage explants [28]. On the other hand, the IL-17 induced production of prostaglandin E2 (PGE2) and nitric oxide (NO) by cartilage explants is LIF-dependent [28,36].…”

Section: Human Studiesmentioning

confidence: 99%

“…On the other hand, the IL-17 induced production of prostaglandin E2 (PGE2) and nitric oxide (NO) by cartilage explants is LIF-dependent [28,36]. Interestingly, an IL-1-independent role of IL-17 in the pathogenesis of experimental arthritis was demonstrated and IL-17 has the capacity to replace the catabolic function of IL-1 in cartilage damage during experimental arthritis [8,37]. Moreover, IL-17 acts independently of TNF under arthritis conditions with no direct role for IL-1 [38].…”

Section: Human Studiesmentioning

confidence: 99%

IL-17/Th17 targeting: On the road to prevent chronic destructive arthritis?

Lubberts¹

2008

Cytokine

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Interleukin-17A (IL-17A) contributes to the pathogenesis of arthritis. Data from experimental arthritis indicate IL-17 receptor signaling as a critical pathway in turning an acute synovitis into a chronic destructive arthritis. The identification of six IL-17 family members (IL-17A-F) may extend the role of this novel cytokine family in the pathogenesis of chronic destructive joint inflammation. Whether the successful anti-IL-17A cytokine therapy in murine arthritis can be effectively translated to human arthritis need to be tested in clinical trials in humans. Interestingly, IL-17A and IL-17F are secreted by the novel T helper subset named Th17. This novel pathogenic T cell population induces autoimmune inflammation in mice and is far more efficient at inducing Th1-mediated autoimmune inflammation in mice than classical Th1 cells (IFN-c). In addition to IL-17A and IL-17F, Th17 cells are characterized by expression of IL-6, TNF, GM-CSF, IL-21, IL-22 and IL-26. Th17 cells have been established as a separate lineage of T helper cells in mice distinct from conventional Th1 and Th2 cells. Whether this also applies to human Th17 and whether RA is a Th1 or a Th17 mediated disease is still not clear. This review summarizes the findings about the role of IL-17 in arthritis and discusses the impact of the discovery of the novel Th17 cells for arthritis. Further studies are needed to unravel the role of Th17 cells and the interplay of IL-17 and other Th17 cytokines in the pathogenesis of arthritis and whether regulating Th17 cell activity will have additional value compared to neutralizing IL-17A activity alone. This might help to reach the ultimate goal not only to treat RA patients but to prevent the development of this crippling disease.

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“…In addition, it was demonstrated that adoptive transfer of IL-23-polarized autoantigen-specific Th17 effector cells were able to transfer EAE more effectively than Th1 cells [9]. IL-17 and IL-23 have also been shown to have a role in the pathogenesis of CIA [10] and colitis [11,12]. These studies established a pathogenic role for Th17 cells in organ-specific autoimmune and chronic inflammatory diseases.…”

mentioning

confidence: 94%

Induction, function and regulation of IL‐17‐producing T cells

2008

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Recent reports have provided convincing evidence that IL-17-producing T cells play a key role in the pathogenesis of organ-specific autoimmune diseases, a function previously attributed exclusively to IFN-c-secreting Th1 cells. Furthermore, it appears that IL-17-producing T cells can also function with Th1 cells to mediate protective immunity to pathogens. Although much of the focus has been on IL-17-secreting CD4 1 T cells, termed The main function of IL-17-secreting T cells is to mediate inflammation, by stimulating production of inflammatory cytokines, such as TNF-a, IL-1b and IL-6, and inflammatory chemokines that promote the recruitment of neutrophils and macrophages.Key words: Autoimmunity . IL-17 . Infection . Inflammation IntroductionMore than 20 years ago Mosmann and Coffman reported that distinct CD4 1 T-cell subtypes, termed Th1 and Th2 cells, could be distinguished on the basis of cytokine secretion and function [1]. The Th1-Th2 model provided a useful but simplistic basis for our understanding of the mechanisms of immunity to infection and also attempted to explain the role of T cells in the pathogenesis of autoimmunity and allergy/asthma. The original hypothesis was that IFN-g-secreting CD4 1 cells mediated protective immunity to intracellular pathogens by promoting macrophage activation and stimulating production of complement fixing and virus neutralizing antibodies, but also promoted inflammatory responses and mediated the pathology in certain autoimmune diseases. In contrast, CD4 1 T cells that secreted IL-4, IL-5, IL-10 and IL-13 were considered to be the main helper T cells providing help for B-cell production of antibody, especially IgG1 in mice, and mediated protective immunity to extracellular pathogens. These Th2 cells were also anti-inflammatory, controlling Th1 responses, but at the same time mediated allergic reactions and had an inflammatory and pathological role in asthma.The identification of additional T-cell subtypes has led to a shift in the Th1-Th2 paradigm and has helped to explain some anomalies in the original model. In the mid 1990s suppressor T cells were re-discovered as Treg cells and were shown to have a major role in controlling immune responses to self-antigens, thereby preventing autoimmunity. Furthermore, these cells rather than the reciprocal Th1 or Th2 populations were shown to be the major regulator of effector T cells, functioning to maintain self-tolerance, prevent autoimmunity and limit collateral damage during immune responses to pathogens [2,3].There were a number of other observations which could not be explained on the basis of the two Th1 and Th2 subtypes. Mini-ReviewDespite the assumption that Th1 cells mediated autoimmunity, mice deficient in IFN-g or IFN-g receptors were found to have increased susceptibility to EAE and collagen-induced arthritis (CIA) [4,5]. Furthermore, EAE was exacerbated in mice deficient in the Th1 polarizing cytokine, 7]. It was then discovered that mice deficient in the novel IL-12 family member, IL-23 were resistant to EAE [6]....

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Induction of cartilage damage by overexpression of T cell interleukin‐17A in experimental arthritis in mice deficient in interleukin‐1

Cited by 90 publications

References 42 publications

Shift from toll‐like receptor 2 (TLR‐2) toward TLR‐4 dependency in the erosive stage of chronic streptococcal cell wall arthritis coincident with TLR‐4–mediated interleukin‐17 production

Shift from toll‐like receptor 2 (TLR‐2) toward TLR‐4 dependency in the erosive stage of chronic streptococcal cell wall arthritis coincident with TLR‐4–mediated interleukin‐17 production

IL-17/Th17 targeting: On the road to prevent chronic destructive arthritis?

Induction, function and regulation of IL‐17‐producing T cells

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