18 research outputs found
The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans
No full textIL-23 and Th17 cells are key players in tissue immunosurveillance and are implicated in human immune-mediated diseases. Genome-wide association studies have shown that the IL23R R381Q gene variant protects against psoriasis, Crohn's disease and ankylosing spondylitis. We investigated the immunological consequences of the protective IL23R R381Q gene variant in healthy donors. The IL23R R381Q gene variant had no major effect on Th17 cell differentiation as the frequency of circulating Th17 cells was similar in carriers of the IL23R protective (A) and common (G) allele. Accordingly, Th17 cells generated from A and G donors produced similar amounts of Th17 cytokines. However, IL-23-mediated Th17 cell effector function was impaired, as Th17 cells from A allele carriers had significantly reduced IL-23-induced IL-17A production and STAT3 phosphorylation compared to G allele carriers. Our functional analysis of a human disease-associated gene variant demonstrates that IL23R R381Q exerts its protective effects through selective attenuation of IL-23-induced Th17 cell effector function without interfering with Th17 differentiation, and highlights its importance in the protection against IL-23-induced tissue pathologies
Tracking changes in the land use, management and drainage status of organic soils as indicators of the effectiveness of mitigation strategies for climate change
No full textAbstractThe tracking of land use since 1990 presents a major challenge in greenhouse gas (GHG) reporting under the United Nations Framework Convention on Climate Change (UNFCCC) and the Kyoto Protocol because there is often limited availability of data, especially for the base year of 1990. There is even less land management and soil moisture data, which are needed to track climate change mitigation activities since soil moisture is one of the main drivers of GHG emissions of organic soils. Information is also needed for the reporting of land-based activities such as grazing land management or wetland drainage and rewetting of organic soils. Different spatial and thematic resolutions of land-use data produce inconsistent time series with a strong overestimation of land-use change (LUC) if not adequately accounted for. Our aim was to create a consistent time series of land use since 1990 that is in line with GHG reporting under the UNFCCC and the Kyoto Protocol by combining official cadastral data with colour-infrared aerial photography used for biodiversity monitoring in six federal states in northern and eastern Germany. We developed a generic hierarchical classification by land use, management and drainage status, and a translation key for data harmonisation into a consistent time series. This time series enabled the quantification of LUC on organic soils between 1992 and 2013 in a spatially explicit manner. Furthermore we used this time series to develop indicators for changes in land management and drainage to evaluate the success of protection statuses on peatland restoration.The study area encompassed one million hectares, half of which had some type of legal nature protection status. Areas with no protection status tended to become more intensively farmed and drier, while highly protected areas (e.g. Natura 2000) showed the opposite trend. Land-use trends also differed greatly between federal states. In Schleswig-Holstein organic soils tended to become drier during the study period, while in Mecklenburg-Western Pomerania they tended to become wetter overall. The trends and differences in LUC between federal states were linked to German reunification, changes in the European Common Agricultural Policy (CAP) and Germany's Renewable Energy Act (EEG). A large-scale peatland protection programme also had major impact.In conclusion, our study demonstrates how data derived for biodiversity monitoring and other highly detailed land-use data can be used to track changes in land use, management and drainage status in accordance with the reporting requirements under the UNFCCC and the Kyoto Protocol
Fine-grained detection of land use and water table changes on organic soils over the period 1992–2012 using multiple data sources in the Drömling nature park, Germany
No full textAbstractThe construction of consistent time series of land use presents a key challenge when accounting for elective land use-based activities under the Kyoto Protocol (wetland drainage and rewetting (WDR), cropland management (CM) and grazing land management (GM)), in which current land use-driven greenhouse gas emissions are compared to a reference situation in 1990.This case study is the first to demonstrate the feasibility of using high-resolution land-use proxies from different datasets for Kyoto accounting in a data-rich case study region in Germany. The study region is characterised by organic soils and has been subject to significant nature conservation measures, including land-use changes, reductions in land-use intensity and changes in groundwater table depth.A consistent time series of 20 years of land use with a spatial resolution of 0.01ha was created from various fine-grained spatial datasets for organic soils in the Drömling nature park by applying a newly developed ‘translation key’. The translation key accounted for systematic differences in legends and thematic resolution. We also tested whether the land-use datasets served as trustworthy proxies for groundwater table depth.Land use in the Drömling nature park became less intensive during the study period of 1992–2012. The greatest land-use change (142hayear−1, 1.14% year−1) occurred between 2000 and 2008. This was in line with management measures undertaken in the nature park. The centre of the nature park became wetter and there was an increase in the share of grassland and more natural vegetation types.The groundwater table correlated with land use and land-use intensity on organic soils in the study area throughout the entire period. Land-use changes were accompanied by altered groundwater tables, except for the conversion from cropland to grassland.Our study indicates that detailed land-use time series can serve as a semi-quantitative proxy for groundwater depth, but that any robust quantitative assessment of water table changes requires in situ data, e.g. from a network of dipwells. Therefore, the combination of land-use and dipwell data provided an accurate basis for estimating GHG emission reductions from drained organic soils since 1990, which is the centre of the Kyoto activity WDR, but also part of afforestation/reforestation (AR) and deforestation (D), forest management (FM), CM and GM. Even the detailed land-use time series on its own would fulfil the requirements for WDR accounting, although with considerable uncertainty about the drainage status of the organic soils. We present the study area of organic soils as a showcase for combining the difficult issues of monitoring changes in land-use intensity as well as in soil wetness, the latter being most relevant for organic soils. The methodology is equally applicable to and relevant for mineral soils
Investigating the Role of Skin Homing V gamma 9V delta 2 T Cells as Novel Pathogenic Cells in Psoriasis
No full textA Gene-to-Function Analysis of IL-23R Arg381Gln Polymorphism Reveals Impaired IL-17A Production in Th17 Cells
No full textExpression of PD-L1 correlates with pleomorphic morphology and histological patterns of non-small-cell lung carcinomas
No full textMALT lymphoma arising on a background of reactive pulmonary lymphoid hyperplasia in a patient with Systemic Lupus Erythematosus.
No full textInterstitial lung diseases are not infrequently complicated by development of malignancies and whilst most cases are carcinomas, rare cases of lymphoma have been reported,(1 2) these being diffuse large B-cell lymphomas and often associated with connective tissue disorders (CTDs). Reactive pulmonary lymphoid hyperplasia (RPLH), typically in the form of lymphoid interstitial pneumonia (LIP) often arises in patients with CTDs and only rarely shows malignant transformation,(3) with many of the early putative cases of transformation to MALT (mucosa-associated lymphoid tissue) lymphoma from LIP being lymphoma 'de novo'.(4) Herein we present a case of pulmonary non-Hodgkin lymphoma of MALT origin arising on a background RPLH with coexistent amyloidosis, confirmed by immunohistochemical and clonality studies. A 57 year old Caucasian female presented with chest pain and breathlessness at rest. She also described intermittent cough with small amounts of sputum, intermittent sweats, fatigue and joint pain in hands, feet, wrists, knees. She was known to have systemic lupus erythematosus (SLE) and SLE-related antiphospholipid syndrome for which she received immunosuppressive therapy including mycophenolate, prednisolone and hydroxychloroquin. This article is protected by copyright. All rights reserved
Allele-Specific Cytokine Responses at the HLA-C Locus: Implications for Psoriasis
No full textPsoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to tumor necrosis factor (TNF)-α (rs2524094) and IFN-γ (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-α and IFN-γ. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-α levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to upregulation by key proinflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele
Author Response: Analytic Formulas on Factors Determining the Safety and Efficacy in UV-Light-Sensitized Corneal Cross-Linking.
No full textVitamin D3 down‐regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen‐associated molecular patterns
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