共查询到20条相似文献,搜索用时 15 毫秒
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Robertson SA 《Biology of reproduction》2012,86(2):26
The discovery of dynamic populations of regulatory T cells in the corpus luteum opens new possibilities for immune regulation of early pregnancy. 相似文献
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Th17 cells, not IL-17+ γδ T cells, drive arthritic bone destruction in mice and humans 总被引:1,自引:0,他引:1
Pöllinger B Junt T Metzler B Walker UA Tyndall A Allard C Bay S Keller R Raulf F Di Padova F O'Reilly T Horwood NJ Patel DD Littlewood-Evans A 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(4):2602-2612
The mechanism whereby IL-17 drives rheumatoid arthritis remains incompletely understood. We demonstrate that anti-IL-17 therapy in collagen-induced arthritis ameliorates bone damage by reducing the number of osteoclasts in joints. We found equal numbers of CD4(+) Th17 and IL-17 producing γδ T cells in the joints of arthritic mice, and in vitro, both populations similarly induced osteoclastogenesis. However, individual depletion and adoptive transfer studies revealed that in vivo, Th17 cells dominated with regard to bone destruction. Unlike γδ T cells, Th17 cells were found in apposition to tartrate-resistant acid phosphatase positive osteoclasts in subchondral areas of inflamed joints, a pattern reproduced in patient biopsies. This localization was caused by Ag-specific retention, because OVA-primed Th17 cells showed a γδ T cell-like diffuse distribution. Because IL-23, as produced by osteoclasts, enhanced T cell-mediated osteoclastogenesis, we propose that Ag-specific juxtaposition is key to foster the molecular cross talk of Th17 cells and osteoclasts, thus driving arthritic bone destruction. 相似文献
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RING for destruction? 总被引:26,自引:0,他引:26
Freemont PS 《Current biology : CB》2000,10(2):R84-R87
Ubiquitination targets proteins for degradation and is a potent regulator of cellular protein function. Recent results implicate the RING finger domain in specific ubiquitination events; it is possible that all RING proteins act as E3 ubiquitin protein ligases, with implications for a variety of biological areas. 相似文献
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Five to six hundred millions of people, throughout the world, suffer from malaria and more than one million die each year as a consequence, in about 20% of the cases, of cerebral malaria, an important complication of Plasmodium falciparum infection (Holding & Snow, 2001). Despite many studies, the physiopathology of these cerebral occurrences is not understood, especially concerning the intricacy and respective roles of the various mechanisms identified: sequestration of parasitized red cells in microvessels, cytokine secretion, changes in the T lymphocyte repertoire, host genetic factors driving sensitivity pathogenic factors from Plasmodium (Mazier et al., 2000). 相似文献
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Martelli AM Faenza I Billi AM Falà F Cocco L Manzoli L 《Histology and histopathology》2003,18(4):1301-1312
Protein kinase C (PKC) isozymes are a family of serine/threonine protein kinases categorized into three subfamilies: classical, novel, and atypical. PKC isozymes, whose expression is cell type-specific and developmentally regulated, are key transducers in many agonist-induced signaling cascades. To date at least 10 different PKC isotypes have been identified and are believed to play distinct regulatory roles. PKC isoforms are catalytically activated by several lipid cofactors, including diacylglycerol. PKC is thought to reside in the cytoplasm in an inactive conformation and to translocate to the plasma membrane or cytoplasmic organelles upon cell activation by different stimuli. However, a sizable body of evidence collected over the last 15 years has shown PKC to be capable of translocating to the nucleus. Furthermore, PKC isoforms can reside within the nucleus. Studies from independent laboratories have to led to the identification of several nuclear proteins which act as PKC substrates as well as to the characterization of some nuclear PKC-binding proteins which may be of fundamental importance for finely tuning PKC function in this peculiar cell microenvironment. Most likely, nuclear PKC isozymes are involved in the regulation of several important biological processes such as cell proliferation and differentiation, neoplastic transformation, and apoptosis. In this review, we shall summarize the most intriguing evidence about the roles played by nuclear PKC isozymes. 相似文献
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Kristina Forslind Johan K?lvesten Ingi?ld Hafstr?m Bj?rn Svensson 《Arthritis research & therapy》2012,14(5):R219
Introduction
The aim of this study was to investigate the role of hand bone mineral density (BMD) loss analyzed with digital X-ray radiogrammetry (DXR) in early rheumatoid arthritis (RA) as a predictor for progression of joint damage.Methods
In 379 patients with early RA, baseline and one-year hand BMD was measured with DXR and the hand bone loss (HBL) was analyzed using the smallest detectable change (HBLsdc) and tertiles (HBLtertiles). Joint damage in hands and feet were scored according to the Sharp van der Heijde (SHS) method at baseline and at one, two, five and eight years. At the same time-points Disease Activity Score (DAS28) was calculated and functional disability assessed. Rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP) were analyzed at baseline.Results
Sixty-six percent of the patients had hand BMD loss in the first year of RA determined by HBLsdc and 65% by HBLtertiles. Radiographic progression after two, five and eight years was associated with hand bone loss defined by HBLsdc. By HBLtertiles there were significant associations at all time-points except at eight years. The change in DXR at one year (ChDXR1yr) correlated significantly and inversely with the change in SHS (ChSHS) at two, five and eight years. Multivariate analysis showed that only change in SHS during the first year and the presence of anti-CCP were independent predictors of long-term progressive joint damage. If radiographic scores were not included, DXR-BMD loss was an independent predictor. Patients with great bone loss by HBLtertiles had significantly more often high disease activity after two years. However, neither bone loss by HBLsdc or HBLtertiles nor by ChDXR1yr was an independent predictor of remission after two, five and eight years.Conclusions
This study confirms previous reports of an association of decrease in DXR-BMD during the first disease year with progression of radiographic joint damage over an extended period of time. This association was independent in a regression model only when radiological findings were excluded suggesting a possible predictive role of DXR-BMD in clinical practice when radiographic evaluation is not available. However, further studies are required before this can be established. 相似文献15.
Beerling DJ 《Trends in ecology & evolution》1998,13(8):311-316
Continued increase in the concentration of atmospheric CO(2) and its possible effects on global climate has generated intense research interest on the likely responses of terrestrial plants and vegetation. Results from this new research provide quantitative information on plant function and growth in an environment with a high CO(2) concentration, but are also relevant to understanding plant growth in the distant past and to the techniques employed by palaeobotanists for reconstructing past climates from fossil plant remains. Experimental CO(2) enrichment of plants has demonstrated direct effects on leaf physiognomy, the tolerance of plants to low temperature and the relationship between tree rings, CO(2) and climate; it therefore signals the need for caution in interpreting palaeoclimates from fossils. 相似文献
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Bendersky A Marcu-Malina V Berkun Y Gerstein M Nagar M Goldstein I Padeh S Bank I 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(9):4349-4359
The pathogenesis of juvenile idiopathic arthritis (JIA) is thought to involve multiple components of the cellular immune system, including subsets of γδ T cells. In this study, we conducted experiments to define the functional roles of one of the major synovial fluid (SF) T cell subsets, Vγ9(+)Vδ2(+) (Vγ9(+)) T cells, in JIA. We found that as opposed to CD4(+) T cells, equally high percentages (~35%) of Vγ9(+) T cells in SF and peripheral blood (PB) produced TNF-α and IFN-γ. Furthermore, stimulation with isopentenyl pyrophosphate (IPP), a metabolite in the mevalonate pathway, which is a specific potent Ag for Vγ9Jγ1.2(+) T cells, similarly amplified cytokine secretion by SF and PB Vγ9(+) T cells. Significantly, the SF subset expressed higher levels of CD69 in situ, suggesting their recent activation. Furthermore, 24-h coculturing with SF-derived fibroblasts enhanced CD69 on the SF > PB Vγ9(+) T cells, a phenomenon strongly augmented by zoledronate, a farnesyl pyrophosphate synthase inhibitor that increases endogenous intracellular IPP. Importantly, although Vγ9(+) T cell proliferation in response to IPP was significantly lower in SF than PBMC cultures, it could be enhanced by depleting SF CD4(+)CD25(+)FOXP3(+) cells (regulatory T cells). Furthermore, coculture with the Vγ9(+) T cells in medium containing zoledronate or IPP strongly increased SF-derived fibroblasts' apoptosis. The findings that IPP-responsive proinflammatory synovial Vγ9(+) T cells for which proliferation is partly controlled by regulatory T cells can recognize and become activated by SF fibroblasts and then induce their apoptosis suggest their crucial role in the pathogenesis and control of synovial inflammation. 相似文献
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Yvonne Vercoulen Nienke H van Teijlingen Ismé M de Kleer Sylvia Kamphuis Salvatore Albani Berent J Prakken 《Arthritis research & therapy》2009,11(3):231-10
Juvenile idiopathic arthritis (JIA) is a disease characterized by chronic joint inflammation, caused by a deregulated immune
response. In patients with JIA, heat shock proteins (HSPs) are highly expressed in the synovial lining tissues of inflamed
joints. HSPs are endogenous proteins that are expressed upon cellular stress and are able to modulate immune responses. In
this review, we concentrate on the role of HSPs, especially HSP60, in modulating immune responses in both experimental and
human arthritis, with a focus on JIA. We will mainly discuss the tolerogenic immune responses induced by HSPs, which could
have a beneficial effect in JIA. Overall, we will discuss the immune modulatory capacity of HSPs, and the underlying mechanisms
of HSP60-mediated immune regulation in JIA, and how this can be translated into therapy. 相似文献