| 1. |
- Zetterqvist, Anna, et al.
(författare)
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Inhibition of nuclear factor of activated T-cells (NFAT) suppresses accelerated atherosclerosis in diabetic mice.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic patients have a much more widespread and aggressive form of atherosclerosis and therefore, higher risk for myocardial infarction, peripheral vascular disease and stroke, but the molecular mechanisms leading to accelerated damage are still unclear. Recently, we showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin. Here we investigate whether NFAT activation may be a link between diabetes and atherogenesis.
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| 2. |
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| 3. |
- Ström, Åsa, et al.
(författare)
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Involvement of the CD1d-Natural killer T cell pathway in neointima formation after vascular injury
- 2007
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Ingår i: CIRCULATION RESEARCH. - 0009-7330. ; 101:8
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have established that the immune system plays an important role in the development of atherosclerosis. However, its role in regulating the arterial response to mechanical injury is less well studied. Arterial injury is associated with local accumulation of antibodies, and mice lacking functional T and B cells exhibit increased neointima formation, indicating that adaptive immune responses to neoantigens in the damaged tissue modulate the vascular repair process. To study the role of lipid antigen presentation in the arterial response to injury, we analyzed neointima formation in mice deficient in the lipid antigen-presenting molecule CD1d using a carotid collar model. As compared with control mice, neointima formation was reduced by >60% (P<0.01) in CD1d-/- mice. Moreover, carotid injury of wild-type C57BL/6 mice was associated with expansion of CD1d-restricted natural killer T cells in the spleen and accumulation of natural killer T cells in the periadventitial space of injured arteries. The results suggest that presentation of lipid antigens through the CD1d-natural killer T cell pathway modulates vascular repair responses.
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| 4. |
- Zetterqvist, Anna, et al.
(författare)
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Nuclear Factor of Activated T Cells Is Activated in the Endothelium of Retinal Microvessels in Diabetic Mice.
- 2015
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Ingår i: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2015
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of diabetic retinopathy (DR) remains unclear but hyperglycemia is an established risk factor. Endothelial dysfunction and changes in Ca(2+) signaling have been shown to precede the onset of DR. We recently demonstrated that high extracellular glucose activates the Ca(2+)/calcineurin-dependent transcription factor NFAT in cerebral arteries and aorta, promoting the expression of inflammatory markers. Here we show, using confocal immunofluorescence, that NFAT is expressed in the endothelium of retinal microvessels and is readily activated by high glucose. This was inhibited by the NFAT blocker A-285222 as well as by the ectonucleotidase apyrase, suggesting a mechanism involving the release of extracellular nucleotides. Acute hyperglycemia induced by an IP-GTT (intraperitoneal glucose tolerance test) resulted in increased NFATc3 nuclear accumulation and NFAT-dependent transcriptional activity in retinal vessels of NFAT-luciferase reporter mice. In both Akita (Ins2(+/-) ) and streptozotocin- (STZ-) induced diabetic mice, NFAT transcriptional activity was elevated in retinal vessels. In vivo inhibition of NFAT with A-285222 decreased the expression of OPN and ICAM-1 mRNA in retinal vessels, prevented a diabetes driven downregulation of anti-inflammatory IL-10 in retina, and abrogated the increased vascular permeability observed in diabetic mice. Results identify NFAT signaling as a putative target for treatment of microvascular complications in diabetes.
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| 5. |
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| 6. |
- Aggestam, Maria, et al.
(författare)
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How women entrepreneurs build embeddedness : a case study approach
- 2017
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Ingår i: International Journal of Gender and Entrepreneurship. - : Emerald Group Publishing Limited. - 1756-6266 .- 1756-6274. ; 9:3, s. 252-268
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe purpose of this study is to examine how women entrepreneurs are building embeddedness into male-gendered fields and how they are creating embedding in such fields in practice.Design/methodology/approachThe qualitative methodology and three indicative case stories within gastronomic industry are illustrated and analysed.FindingsThe contribution of this study lies in the examination of the multifaceted embedding building process from dis-embedded, marginalised and suppressed position by women entrepreneurs. This was achieved with the help of building embedding through two strategies: sameness, that is, becoming one of the boys and then becoming a challenger, thereby enhancing their professional position.Research limitations/implicationsThe study is subject to limitations; a small sample is not suited for the generalizability of results. The most important implication of this study is the identification of the process of building embeddedness as the most critical resource for women’s entrepreneurship that should be supported by the scholarly and business community.Originality/valueThe theoretical framework developed for this study laid the foundation for developing literature on the embeddedness of women’s entrepreneurship and how the process of creating embedding becomes instrumental in business ownership.
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| 7. |
- Aggestam, Maria, et al.
(författare)
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How women entrepreneurs build embeddedness : a case study approach
- 2017
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Ingår i: International Journal of Gender and Entrepreneurship. - 1756-6266. ; 9:3, s. 252-268
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe purpose of this study is to examine how women entrepreneurs are building embeddedness into male-gendered fields and how they are creating embedding in such fields in practice.Design/methodology/approachThe qualitative methodology and three indicative case stories within gastronomic industry are illustrated and analysed.FindingsThe contribution of this study lies in the examination of the multifaceted embedding building process from dis-embedded, marginalised and suppressed position by women entrepreneurs. This was achieved with the help of building embedding through two strategies: sameness, that is, becoming one of the boys and then becoming a challenger, thereby enhancing their professional position.Research limitations/implicationsThe study is subject to limitations; a small sample is not suited for the generalizability of results. The most important implication of this study is the identification of the process of building embeddedness as the most critical resource for women’s entrepreneurship that should be supported by the scholarly and business community.Originality/valueThe theoretical framework developed for this study laid the foundation for developing literature on the embeddedness of women’s entrepreneurship and how the process of creating embedding becomes instrumental in business ownership.
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| 10. |
- Dao Nyesiga, Gillian, et al.
(författare)
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Tolerogenic dendritic cells generated in vitro using a novel protocol mimicking mucosal tolerance mechanisms represent a potential therapeutic cell platform for induction of immune tolerance.
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) are mediators between innate and adaptive immunity and vital in initiating and modulating antigen-specific immune responses. The most important site for induction of tolerance is the gut mucosa, where TGF-β, retinoic acid, and aryl hydrocarbon receptors collaborate in DCs to induce a tolerogenic phenotype. To mimic this, a novel combination of compounds – the synthetic aryl hydrocarbon receptor (AhR) agonist IGN-512 together with TGF-β and retinoic acid – was developed to create a platform technology for induction of tolerogenic DCs intended for treatment of several conditions caused by unwanted immune activation. These in vitro-generated cells, designated ItolDCs, are phenotypically characterized by their low expression of co-stimulatory and activating molecules along with high expression of tolerance-associated markers such as ILT3, CD103, and LAP, and a weak pro-inflammatory cytokine profile. When co-cultured with T cells and/or B cells, ItolDC-cultures contain higher frequencies of CD25+Foxp3+ regulatory T cells (Tregs), CD49b+LAG3+ ‘type 1 regulatory (Tr1) T cells, and IL-10-producing B cells and are less T cell stimulatory compared to cultures with matured DCs. Factor VIII (FVIII) and tetanus toxoid (TT) were used as model antigens to study ItolDC antigen-loading. ItolDCs can take up FVIII, process, and present FVIII peptides on HLA-DR. By loading both ItolDCs and mDCs with TT, antigen-specific T cell proliferation was observed. Cryo-preserved ItolDCs showed a stable tolerogenic phenotype that was maintained after stimulation with LPS, CD40L, or a pro-inflammatory cocktail. Moreover, exposure to other immune cells did not negatively impact ItolDCs’ expression of tolerogenic markers. In summary, a novel protocol was developed supporting the generation of a stable population of human DCs in vitro that exhibited a tolerogenic phenotype with an ability to increase proportions of induced regulatory T and B cells in mixed cultures. This protocol has the potential to constitute the base of a tolDC platform for inducing antigen-specific tolerance in disorders caused by undesired antigen-specific immune cell activation.
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