468 research outputs found
Overrepresentation of IL-17A and IL-22 Producing CD8 T Cells in Lesional Skin Suggests Their Involvement in the Pathogenesis of Psoriasis
Overrepresentation of IL-17A and IL-22 Producing CD8 T Cells in Lesional Skin Suggests Their Involvement in the Pathogenesis of Psoriasis
Background: Although recent studies indicate a crucial role for IL-17A and IL-22 producing T cells in the pathogenesis of psoriasis, limited information is available on their frequency and heterogeneity and their distribution in skin in situ. Methodology/Principal Findings: By spectral imaging analysis of double-stained skin sections we demonstrated that IL-17 was mainly expressed by mast cells and neutrophils and IL-22 by macrophages and dendritic cells. Only an occasional IL-17(pos), but no IL-22(pos) T cell could be detected in psoriatic skin, whereas neither of these cytokines was expressed by T cells in normal skin. However, examination of in vitro-activated T cells by flow cytometry revealed that substantial percentages of skin-derived CD4 and CD8 T cells were able to produce IL-17A alone or together with IL-22 (i.e. Th17 and Tc17, respectively) or to produce IL-22 in absence of IL-17A and IFN-gamma (i.e. Th22 and Tc22, respectively). Remarkably, a significant proportional rise in Tc17 and Tc22 cells, but not in Th17 and Th22 cells, was found in T cells isolated from psoriatic versus normal skin. Interestingly, we found IL-22 single-producers in many skin-derived IL-17A(pos) CD4 and CD8 T cell clones, suggesting that in vivo IL-22 single-producers may arise from IL-17A(pos) T cells as well. Conclusions/Significance: The increased presence of Tc17 and Tc22 cells in lesional psoriatic skin suggests that these types of CD8 T cells play a significant role in the pathogenesis of psoriasis. As part of the skin-derived IL-17A(pos) CD4 and CD8 T clones developed into IL-22 single-producers, this demonstrates plasticity in their cytokine production profile and suggests a developmental relationship between Th17 and Th22 cells and between Tc17 and Tc22 cell
A quantitative account of genomic island acquisitions in prokaryotes
<p>Abstract</p> <p>Background</p> <p>Microbial genomes do not merely evolve through the slow accumulation of mutations, but also, and often more dramatically, by taking up new DNA in a process called horizontal gene transfer. These innovation leaps in the acquisition of new traits can take place via the introgression of single genes, but also through the acquisition of large gene clusters, which are termed Genomic Islands. Since only a small proportion of all the DNA diversity has been sequenced, it can be hard to find the appropriate donors for acquired genes via sequence alignments from databases. In contrast, relative oligonucleotide frequencies represent a remarkably stable genomic signature in prokaryotes, which facilitates compositional comparisons as an alignment-free alternative for phylogenetic relatedness.</p> <p>In this project, we test whether Genomic Islands identified in individual bacterial genomes have a similar genomic signature, in terms of relative dinucleotide frequencies, and can therefore be expected to originate from a common donor species.</p> <p>Results</p> <p>When multiple Genomic Islands are present within a single genome, we find that up to 28% of these are compositionally very similar to each other, indicative of frequent recurring acquisitions from the same donor to the same acceptor.</p> <p>Conclusions</p> <p>This represents the first quantitative assessment of common directional transfer events in prokaryotic evolutionary history. We suggest that many of the resident Genomic Islands per prokaryotic genome originated from the same source, which may have implications with respect to their regulatory interactions, and for the elucidation of the common origins of these acquired gene clusters.</p
Spong3d: 3D printed facade system enabling movable fluid heat storage
Spong3D is an adaptive 3D printed facade system that integrates multiple functions to optimize thermal performances according to the different environmental conditions throughout the year. The proposed system incorporates air cavities to provide thermal insulation and a movable liquid (water plus additives) to provide heat storage where and whenever needed. The air cavities have various dimensions and are located in the inner part of the system. The movable liquid provides heat storage as it flows through channels located along the outer surfaces of the system (on the indoor and outdoor faces of the façade). Together, the composition of the channels and the cavities form a complex structure, integrating multiple functions into a singular component, which can only be produced by using an Additive Manufacturing (AM; like 3D printing) technology
Spong3d: 3D printed facade system enabling movable fluid heat storage
Spong3D is an adaptive 3D printed facade system that integrates multiple functions to optimize thermal performances according to the different environmental conditions throughout the year. The proposed system incorporates air cavities to provide thermal insulation and a movable liquid (water plus additives) to provide heat storage where and whenever needed. The air cavities have various dimensions and are located in the inner part of the system. The movable liquid provides heat storage as it flows through channels located along the outer surfaces of the system (on the indoor and outdoor faces of the façade). Together, the composition of the channels and the cavities form a complex structure, integrating multiple functions into a singular component, which can only be produced by using an Additive Manufacturing (AM; like 3D printing) technology
Novel human antibody therapeutics: The age of the Umabs
Monoclonal antibodies represent a major and increasingly important category of biotechnology products for the treatment of human diseases. The state-of-the-art of antibody technology has evolved to the point where therapeutic monoclonal antibodies, that are practically indistinguishable from antibodies induced in humans, are routinely generated. We depict how our science-based approach can be used to further improve the efficacy of antibody therapeutics, illustrated by the development of three monoclonal antibodies for various cancer indications: zanolimumab (directed against CD4), ofatumumab (directed against CD20) and zalutumumab (directed against epidermal growth factor receptor)
New insights into the impact of neuro-inflammation in rheumatoid arthritis.
Rheumatoid arthritis (RA) is considered to be, in many respects, an archetypal autoimmune disease that causes activation of pro-inflammatory pathways resulting in joint and systemic inflammation. RA remains a major clinical problem with the development of several new therapies targeted at cytokine inhibition in recent years. In RA, biologic therapies targeted at inhibition of tumor necrosis factor alpha (TNFα) have been shown to reduce joint inflammation, limit erosive change, reduce disability and improve quality of life. The cytokine TNFα has a central role in systemic RA inflammation and has also been shown to have pro-inflammatory effects in the brain. Emerging data suggests there is an important bidirectional communication between the brain and immune system in inflammatory conditions like RA. Recent work has shown how TNF inhibitor therapy in people with RA is protective for Alzheimer's disease. Functional MRI studies to measure brain activation in people with RA to stimulus by finger joint compression, have also shown that those who responded to TNF inhibition showed a significantly greater activation volume in thalamic, limbic, and associative areas of the brain than non-responders. Infections are the main risk of therapies with biologic drugs and infections have been shown to be related to disease flares in RA. Recent basic science data has also emerged suggesting that bacterial components including lipopolysaccharide induce pain by directly activating sensory neurons that modulate inflammation, a previously unsuspected role for the nervous system in host-pathogen interactions. In this review, we discuss the current evidence for neuro-inflammation as an important factor that impacts on disease persistence and pain in RA
TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain
Background:
The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders.
Methods:
Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour.
Results:
We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity.
Conclusions:
These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response
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