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Find video protocols related to scientific articles indexed in Pubmed.
Fc?RIIb on myeloid cells rather than on B cells protects from collagen-induced arthritis.
J. Immunol.
PUBLISHED: 05-19-2014
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Extensive analysis of a variety of arthritis models in germline KO mice has revealed that all four receptors for the Fc part of IgG (Fc?R) play a role in the disease process. However, their precise cell type-specific contribution is still unclear. In this study, we analyzed the specific role of the inhibiting Fc?RIIb on B lymphocytes (using CD19Cre mice) and in the myeloid cell compartment (using C/EBP?Cre mice) in the development of arthritis induced by immunization with either bovine or chicken collagen type II. Despite their comparable anti-mouse collagen autoantibody titers, full Fc?RIIb knockout (KO), but not B cell-specific Fc?RIIb KO, mice showed a significantly increased incidence and severity of disease compared with wild-type control mice when immunized with bovine collagen. When immunized with chicken collagen, disease incidence was significantly increased in pan-myeloid and full Fc?RIIb KO mice, but not in B cell-specific KO mice, whereas disease severity was only significantly increased in full Fc?RIIb KO mice compared with incidence and severity in wild-type control mice. We conclude that, although anti-mouse collagen autoantibodies are a prerequisite for the development of collagen-induced arthritis, their presence is insufficient for disease development. Fc?RIIb on myeloid effector cells, as a modulator of the threshold for downstream Ab effector pathways, plays a dominant role in the susceptibility to collagen-induced arthritis, whereas Fc?RIIb on B cells, as a regulator of Ab production, has a minor effect on disease susceptibility.
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A human vitamin D receptor mutation causes rickets and impaired Th1/Th17 responses.
Bone
PUBLISHED: 03-28-2014
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We present a brother and sister with severe rickets, alopecia and highly elevated serum levels of 1,25-dihydroxyvitamin D (1,25-(OH)2D3). Genomic sequencing showed a homozygous point mutation (A133G) in the vitamin D receptor gene, leading to an amino acid change in the DNA binding domain (K45E), which was described previously. Hereditary vitamin D resistant rickets (HVDRR) was diagnosed. Functional studies in skin biopsy fibroblasts confirmed this. 1,25-(OH)2D3 reduced T helper (Th) cell population-specific cytokine expression of interferon ? (Th1), interleukins IL-17A (Th17) and IL-22 (Th17/Th22) in peripheral blood mononuclear cells (PBMCs) from the patient's parents, whereas IL-4 (Th2) levels were higher, reflecting an immunosuppressive condition. None of these factors were regulated by 1,25-(OH)2D3 in PBMCs from the boy. At present, both patients (boy is 23years of age, girl is 7) have not experienced any major immune-related disorders. Although both children developed alopecia, the girl did so earlier than the boy. The boy showed complete recovery from the rickets at the age of 17 and does not require any vitamin D supplementations to date. In conclusion, we characterized two siblings with HVDRR, due to a mutation in the DNA binding domain of VDR. Despite a defective T cell response to vitamin D, no signs of any inflammatory-related abnormalities were seen, thus questioning an essential role of vitamin D in the immune system. Despite the fact that currently medicine is not required, close monitoring in the future of these patients is warranted for potential recurrence of vitamin D dependence and diagnosis of (chronic) inflammatory-related diseases.
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Absence of interleukin-17 receptor a signaling prevents autoimmune inflammation of the joint and leads to a Th2-like phenotype in collagen-induced arthritis.
PUBLISHED: 02-08-2014
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Interleukin-17A (IL-17A) signals through the IL-17 receptor (IL-17R) A/C heterodimer. IL-17RA serves as a common receptor subunit for several IL-17 cytokine family members. Lack of IL-17RA signaling may therefore have additional effects beyond those of lack of IL-17A alone. The present study was undertaken to determine the role of IL-17RA signaling in autoimmune arthritis.
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Synovial fibroblasts directly induce Th17 pathogenicity via the cyclooxygenase/prostaglandin E2 pathway, independent of IL-23.
J. Immunol.
PUBLISHED: 07-01-2013
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Th17 cells are critically involved in autoimmune disease induction and severity. Recently, we showed that Th17 cells from patients with rheumatoid arthritis (RA) directly induced a proinflammatory loop upon interaction with RA synovial fibroblasts (RASF), including increased autocrine IL-17A production. To unravel the mechanism driving this IL-17A production, we obtained primary CD4(+)CD45RO(+)CCR6(+) (Th17) cells and CD4(+)CD45RO(+)CCR6(-) (CCR6(-)) T cells from RA patients or healthy individuals and cocultured these with RASF. IL-1?, IL-6, IL-23p19, and cyclooxygenase (COX)-2 expression and PGE2 production in Th17-RASF cultures were higher than in CCR6(-) T cell-RASF cultures. Cytokine neutralization showed that IL-1? and IL-6, but not IL-23, contributed to autocrine IL-17A induction. Importantly, treatment with celecoxib, a COX-2 inhibitor, resulted in significantly lower PGE2 and IL-17A, but not IFN-?, production. Combined celecoxib and TNF-? blockade more effectively suppressed the proinflammatory loop than did single treatment, as shown by lower IL-6, IL-8, matrix metalloproteinase-1 and matrix metalloproteinase-3 production. These findings show a critical role for the COX-2/PGE2 pathway in driving Th17-mediated synovial inflammation in an IL-23- and monocyte-independent manner. Therefore, it would be important to control PGE2 in chronic inflammation in RA and potentially other Th17-mediated autoimmune disorders.
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IL-23 dependent and independent stages of experimental arthritis: no clinical effect of therapeutic IL-23p19 inhibition in collagen-induced arthritis.
PLoS ONE
PUBLISHED: 01-25-2013
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IL-23p19 deficient mice have revealed a critical role of IL-23 in the development of experimental autoimmune diseases, such as collagen-induced arthritis (CIA). Neutralizing IL-23 after onset of CIA in rats has been shown to reduce paw volume, but the effect on synovial inflammation and the immunological autoimmune response is not clear. In this study, we examined the role of IL-23 at different stages of CIA and during T cell memory mediated flare-up arthritis with focus on changes in B cell activity and Th1/Th17 modulation. Anti-IL-23p19 antibody (anti-IL23p19) treatment, starting 15 days after the type II collagen (CII)-immunization but before clinical signs of disease onset, significantly suppressed the severity of CIA. This was accompanied with significantly lower CII-specific IgG1 levels and lower IgG2a levels in the anti-IL-23p19 treated mice compared to the control group. Importantly, neutralizing IL-23 after the first signs of CIA did not ameliorate the disease. This was in contrast to arthritic mice that underwent an arthritis flare-up since a significantly lower disease score was observed in the IL-23p19 treated mice compared to the control group, accompanied by lower synovial IL-17A and IL-22 expression in the knee joints of these mice. These data show IL-23-dependent and IL-23-independent stages during autoimmune CIA. Furthermore, the memory T cell mediated flare-up arthritis is IL-23-mediated. These data suggest that specific neutralization of IL-23p19 after onset of autoimmune arthritis may not be beneficial as a therapeutic therapy for patients with rheumatoid arthritis (RA). However, T cell mediated arthritis relapses in patients with RA might be controlled by anti-IL-23p19 treatment.
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IL-17/Th17 mediated synovial inflammation is IL-22 independent.
Ann. Rheum. Dis.
PUBLISHED: 01-17-2013
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Interleukin (IL)-17A and Th17 cells are critically involved in T cell-mediated synovial inflammation. Besides IL-17A, Th17 cells produce IL-22. Recently, Th22 cells were discovered, which produce IL-22 in the absence of IL-17. However, it remains unclear whether IL-22 and Th22 cells contribute to T cell-mediated synovial inflammation. Therefore, we examined the potential of IL-22 and Th22 cells to induce synovial inflammation and whether IL-22 is required for T cell-mediated experimental arthritis.
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Interleukin-23 promotes Th17 differentiation by inhibiting T-bet and FoxP3 and is required for elevation of interleukin-22, but not interleukin-21, in autoimmune experimental arthritis.
Arthritis Rheum.
PUBLISHED: 02-05-2010
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To examine the role of interleukin-23 (IL-23) in subgroup polarization of IL-17A-positive and/or interferon-gamma (IFNgamma)-positive T cells in autoimmune disease-prone DBA/1 mice with and without collagen-induced arthritis.
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Interleukin-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates interleukin-17A and RORgammat in gammadelta T cells.
Arthritis Res. Ther.
PUBLISHED: 08-19-2009
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Interleukin (IL)-23 is essential for the development of various experimental autoimmune models. However, the role of IL-23 in non-autoimmune experimental arthritis remains unclear. Here, we examined the role of IL-23 in the non-autoimmune antigen-induced arthritis (AIA) model. In addition, the regulatory potential of IL-23 in IL-17A and retinoic acid-related orphan receptor gamma t (RORgammat) expression in CD4+ and TCRgammadelta+ T cells was evaluated systemically as well as at the site of inflammation.
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GATA-3 protects against severe joint inflammation and bone erosion and reduces differentiation of Th17 cells during experimental arthritis.
Arthritis Rheum.
PUBLISHED: 02-28-2009
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Rheumatoid arthritis is associated with the infiltration of T helper cells into the joints. It is unclear whether interferon-gamma (IFNgamma)-producing Th1 cells or the novel T helper subset, interleukin-17 (IL-17)-producing Th17 cells, are the pathogenic mediators of joint inflammation in chronic nonautoimmune arthritis. Therefore, this study was aimed at examining whether the Th2-specific transcription factor GATA-3 can regulate arthritis, in an experimental murine model, by modulating Th1 and/or Th17 cell polarization.
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TNF blockade requires 1,25(OH)2D3 to control human Th17-mediated synovial inflammation.
Ann. Rheum. Dis.
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T helper 17 (Th17) cells from patients with early rheumatoid arthritis (RA) induce a proinflammatory feedback loop upon RA synovial fibroblast (RASF) interaction, including autocrine interleukin (IL)-17A production. A major challenge in medicine is how to control the pathogenic Th17 cell activity in human inflammatory autoimmune diseases. The objective of this study was to examine whether tumour necrosis factor (TNF) blockade and/or 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) controls Th17-mediated synovial inflammation.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.