| 1. |
- Grunewald, Johan, et al.
(författare)
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T-cell receptor-HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis
- 2016
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 47:3, s. 898-909
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Tidskriftsartikel (refereegranskat)abstract
- In pulmonary sarcoidosis, CD4(+) T-cells expressing T-cell receptor V alpha 2.3 accumulate in the lungs of HLA-DRB1*03(+) patients. To investigate T-cell receptor-HLA-DRB1*03 interactions underlying recognition of hitherto unknown antigens, we performed detailed analyses of T-cell receptor expression on bronchoalveolar lavage fluid CD4(+) T-cells from sarcoidosis patients. Pulmonary sarcoidosis patients (n=43) underwent bronchoscopy with bronchoalveolar lavage. T-cell receptor alpha and beta chains of CD4(+) T-cells were analysed by flow cytometry, DNA-sequenced, and three-dimensional molecular models of T-cell receptor-HLA-DRB1*03 complexes generated. Simultaneous expression of V alpha 2.3 with the V beta 22 chain was identified in the lungs of all HLA-DRB1*03(+) patients. Accumulated V alpha 2.3/V beta 22-expressing T-cells were highly clonal, with identical or near-identical V alpha 2.3 chain sequences and inter-patient similarities in V beta 22 chain amino acid distribution. Molecular modelling revealed specific T-cell receptor-HLA-DRB1*03-peptide interactions, with a previously identified, sarcoidosis-associated vimentin peptide, (Vim)(429-443) DSLPLVDTHSKRTLL, matching both the HLA peptide-binding cleft and distinct T-cell receptor features perfectly. We demonstrate, for the first time, the accumulation of large clonal populations of specific V alpha 2.3/V beta 22 T-cell receptor-expressing CD4(+) T-cells in the lungs of HLA-DRB1*03(+) sarcoidosis patients. Several distinct contact points between V alpha 2.3/V beta 22 receptors and HLA-DRB1*03 molecules suggest presentation of prototypic vimentin-derived peptides.
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| 2. |
- Pejler, Gunnar
(författare)
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The emerging role of mast cell proteases in asthma
- 2019
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Ingår i: European Respiratory Journal. - 0903-1936 .- 1399-3003. ; 54
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Tidskriftsartikel (refereegranskat)abstract
- It is now well established that mast cells play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on mast cell-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which mast cells influence asthma pathology. Mast cells contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of mast cell-restricted proteases. When mast cells are activated, e.g. in response to IgE receptor crosslinking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The mast cell-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels. There is now emerging evidence supporting a prominent role of these enzymes in the pathology of asthma. Interestingly though, the role of the mast cell-restricted proteases is multifaceted, encompassing both protective and detrimental activities. Here, I review the current knowledge of how the mast cell-restricted proteases impact on asthma.
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| 3. |
- Pellegrino, R, et al.
(författare)
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Interpretative strategies for lung function tests.
- 2005
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Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 0903-1936. ; 26:5, s. 948-68
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Sigsgaard, Torben, et al.
(författare)
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Health impacts of anthropogenic biomass burning in the developed world.
- 2015
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 46:6, s. 1577-1588
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Tidskriftsartikel (refereegranskat)abstract
- Climate change policies have stimulated a shift towards renewable energy sources such as biomass. The economic crisis of 2008 has also increased the practice of household biomass burning as it is often cheaper than using oil, gas or electricity for heating. As a result, household biomass combustion is becoming an important source of air pollutants in the European Union.This position paper discusses the contribution of biomass combustion to pollution levels in Europe, and the emerging evidence on the adverse health effects of biomass combustion products.Epidemiological studies in the developed world have documented associations between indoor and outdoor exposure to biomass combustion products and a range of adverse health effects. A conservative estimate of the current contribution of biomass smoke to premature mortality in Europe amounts to at least 40000 deaths per year.We conclude that emissions from current biomass combustion products negatively affect respiratory and, possibly, cardiovascular health in Europe. Biomass combustion emissions, in contrast to emissions from most other sources of air pollution, are increasing. More needs to be done to further document the health effects of biomass combustion in Europe, and to reduce emissions of harmful biomass combustion products to protect public health.
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