Regulation of CD154-induced interleukin-12 production in synovial fluid macrophages

Möttönen, M.; Isomäki, Pia; Luukkainen, R; Lassila, O.

doi:10.1186/ar589

Cited by 10 publications

(3 citation statements)

References 40 publications

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“…Here we hypothesize that IL-12p40 could be considered as immunological biomarker in the evaluation of synovitis in this animal model. Supporting this statement, similar changes have been observed in the synovial tissue of rheumatoid arthritis patients where increased IL-12p40 levels have been detected [37]. …”

Section: Discussionsupporting

confidence: 80%

Evaluation of antigen-induced synovitis in a porcine model: Immunological, arthroscopic and kinetic studies

et al. 2017

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BackgroundSynovitis is an inflammation-related disease linked to rheumatoid arthritis, osteoarthritis, infections and trauma. This inflammation is accompanied by immune cells infiltration which initiates an inflammatory response causing pain, discomfort and affecting the normal joint function. The treatment of synovitis is based on the administration of anti-inflammatory drugs or biological agents such as platelet rich plasma and mesenchymal stem cells. However, the evaluation and validation of more effective therapies of synovitis requires the establishment of clinically relevant animal models.ResultsIn this study, Large White pigs were pre-immunized to evaluate an antigen-induced synovitis. The immune monitoring of synovial fluids in this model allowed us the identification of IL-12p40 and T cell subsets as immune biomarkers. Moreover, the evolution of synovitis was performed by arthroscopic procedures and kinetic analysis. In summary, this paper describes an animal model of antigen-induced synovitis to be used in the evaluation of anti-inflammatory therapies.ConclusionsThe novelty of this paper lies in the development of a clinically relevant model of synovitis which permits the simultaneous evaluation of synovitis from an immunological, surgical and kinetic point of view.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-017-1025-4) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 80%

Evaluation of antigen-induced synovitis in a porcine model: Immunological, arthroscopic and kinetic studies

et al. 2017

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“…The IL-21 receptor is expressed by all NK cells in the blood, and IL-21 stimulates NK cell survival, cytotoxicity and IFN-γ secretion [30] . The synovial fluid of RA patients has been found to contain high levels of IL-12 [45] , IL-18 [46] , IL-15 [47] , IL-7 [48] and IL-21 [49] , and cytokines such as IL-12, IL-18 and IFN-α are produced by activated DCs and macrophages and have also been implicated in chronic inflammation [30] , making it plausible that NK cells, in a chronic inflammatory setting, can become activated by several cytokines. It is interesting to highlight that regardless of how NK cells were activated, the same activating and inhibitory receptors controlled degranulation of NK cells in response to activated autologous CD4 + T cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity of CD56bright NK Cells towards Autologous Activated CD4+ T Cells Is Mediated through NKG2D, LFA-1 and TRAIL and Dampened via CD94/NKG2A

et al. 2012

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In mouse models of chronic inflammatory diseases, Natural Killer (NK) cells can play an immunoregulatory role by eliminating chronically activated leukocytes. Indirect evidence suggests that NK cells may also be immunoregulatory in humans. Two subsets of human NK cells can be phenotypically distinguished as CD16+CD56dim and CD16dim/−CD56bright. An expansion in the CD56bright NK cell subset has been associated with clinical responses to therapy in various autoimmune diseases, suggesting an immunoregulatory role for this subset in vivo. Here we compared the regulation of activated human CD4+ T cells by CD56dim and CD56bright autologous NK cells in vitro. Both subsets efficiently killed activated, but not resting, CD4+ T cells. The activating receptor NKG2D, as well as the integrin LFA-1 and the TRAIL pathway, played important roles in this process. Degranulation by NK cells towards activated CD4+ T cells was enhanced by IL-2, IL-15, IL-12+IL-18 and IFN-α. Interestingly, IL-7 and IL-21 stimulated degranulation by CD56bright NK cells but not by CD56dim NK cells. NK cell killing of activated CD4+ T cells was suppressed by HLA-E on CD4+ T cells, as blocking the interaction between HLA-E and the inhibitory CD94/NKG2A NK cell receptor enhanced NK cell degranulation. This study provides new insight into CD56dim and CD56bright NK cell-mediated elimination of activated autologous CD4+ T cells, which potentially may provide an opportunity for therapeutic treatment of chronic inflammation.

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“…LIGHT is expressed in CD68 + macrophages and in vitro stimulation of these cells with LIGHT induced expression of MMP-9 and pro-inflammatory cytokines TNF-α, IL-6, and IL-8 [ 36 ]. Synovial fluid macrophages express increased levels of CD40 and produce both IL-12p40, TNF-α and IL-10 after CD40 ligation [ 37 ]. However, the contribution of the non-canonical NF-κB pathway to these LIGHT- and CD40L-induced processes remains to be tested.…”

Section: Non-canonical Nf-κb Signaling In Rheumatoid Arthritismentioning

confidence: 99%

Non-canonical NF-κB signaling in rheumatoid arthritis: Dr Jekyll and Mr Hyde?

2015

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The nuclear factor-κB (NF-κB) family of transcription factors is essential for the expression of pro-inflammatory cytokines, but can also induce regulatory pathways. NF-κB can be activated via two distinct pathways: the classical or canonical pathway, and the alternative or non-canonical pathway. It is well established that the canonical NF-κB pathway is essential both in acute inflammatory responses and in chronic inflammatory diseases, including rheumatoid arthritis (RA). Although less extensively studied, the non-canonical NF-κB pathway is not only central in lymphoid organ development and adaptive immune responses, but is also thought to play an important role in the pathogenesis of RA. Importantly, this pathway appears to have cell type-specific functions and, since many different cell types are involved in the pathogenesis of RA, it is difficult to predict the net overall contribution of the non-canonical NF-κB pathway to synovial inflammation. In this review, we describe the current understanding of non-canonical NF-κB signaling in various important cell types in the context of RA and consider the relevance to the pathogenesis of the disease. In addition, we discuss current drugs targeting this pathway, as well as future therapeutic prospects.

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Regulation of CD154-induced interleukin-12 production in synovial fluid macrophages

Cited by 10 publications

References 40 publications

Evaluation of antigen-induced synovitis in a porcine model: Immunological, arthroscopic and kinetic studies

Evaluation of antigen-induced synovitis in a porcine model: Immunological, arthroscopic and kinetic studies

Cytotoxicity of CD56bright NK Cells towards Autologous Activated CD4+ T Cells Is Mediated through NKG2D, LFA-1 and TRAIL and Dampened via CD94/NKG2A

Non-canonical NF-κB signaling in rheumatoid arthritis: Dr Jekyll and Mr Hyde?

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