a-method-for-generating-pulmonary-neutrophilia-using-aerosolized

A Method for Generating Pulmonary Neutrophilia Using Aerosolized Lipopolysaccharide

Acute lung injury (ALI) is a severe disease characterized by alveolar neutrophilia, with limited treatment options and high mortality. Experimental models ...

Karolinska Institutet

Epoxide hydrolases catalyze the conversion of epoxides to diols. The known functions of such enzymes include detoxification of xenobiotics, drug metabolism, synthesis of signaling compounds, and intermediary metabolism. In plants, epoxide hydrolases are thought to participate in general defense systems. In the present study, we report the first structure of a plant epoxide hydrolase, one of the four homologous enzymes found in potato. The structure was solved by molecular replacement and refined to a resolution of 1.95 A. Analysis of the structure allows a better understanding of the observed substrate specificities and activity. Further, comparisons with mammalian and fungal epoxide hydrolase structures reported earlier show the basis of differing substrate specificities in the various epoxide hydrolase subfamilies. Most plant enzymes, like the potato epoxide hydrolase, are expected to be monomers with a preference for substrates with long lipid-like substituents of the epoxide ring. The significance of these results in the context of biological roles and industrial applications is discussed.

X-ray structure of potato epoxide hydrolase sheds light on substrate specificity in plant enzymes.

Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure are hallmarks of the disease. The critical mechanisms causing chronic mucocutaneous candidiasis in APS-1 patients have not been identified although autoantibodies to cytokines are implicated in the pathogenesis. To investigate whether the Th reactivity to Candida albicans (C. albicans) and other stimuli was altered, we isolated PBMC from APS-1 patients and matched healthy controls. The Th17 pathway was upregulated in response to C. albicans in APS-1 patients, whereas the IL-22 secretion was reduced. Autoantibodies against IL-22, IL-17A and IL-17F were detected in sera from APS-1 patients by immunoprecipitation. In addition, Aire-deficient (Aire(0/0) ) mice were much more susceptible than Aire(+/+) mice to mucosal candidiasis and C. albicans-induced Th17- and Th1-cell responses were increased in Aire(0/0) mice. Thus an excessive IL-17A reactivity towards C. albicans was observed in APS-1 patients and Aire(0/0) mice.

Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model.

EAE, an animal model for multiple sclerosis, is a Th17- and Th1-cell-mediated auto-immune disease, but the mechanisms leading to priming of encephalitogenic T cells in autoimmune neuroinflammation are poorly understood. To investigate the role of dendritic cells (DCs) in the initiation of autoimmune Th17- and Th1-cell responses and EAE, we used mice transgenic for a simian diphtheria toxin receptor (DTR) expressed under the control of the murine CD11c promoter (CD11c-DTR mice o nC57BL/6 background).EAE was induced by immunization with myelin oligodendrocyte glycoprotein (MOG) protein in CFA. DCs were depleted on the day before and 8 days after MOG immunization. The mean clinical EAE score was only mildly reduced in DC-depleted mice when DCs were ablated before EAE induction. The frequency of activated Th cells was not altered, and MOG-induced Th17 or Th1-cell responses were not altered, in the spleens of DC-depleted mice. Similar results were obtained if DCs were ablated the first 10 days after MOG immunization with repeated DC depletions. Unexpectedly, transient depletion of DCs did not affect priming or differentiation of MOG-induced Th17 and Th1-cell responses or the incidence of EAE. Thus, the mechanism of priming of Th cells in EAE remains to be elucidated.

Conditional DC depletion does not affect priming of encephalitogenic Th cells in EAE.

Sarcoidosis patients have accumulations of activated CD4+ T cells in affected organs, such as the lungs. T cell receptor (TCR) Vβ-chain usage has been incompletely characterized in these patients.

T cell receptor-Vβ repertoires in lung and blood CD4+ and CD8+ T cells of pulmonary sarcoidosis patients.

Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.

Article	Year
X-ray structure of potato epoxide hydrolase sheds light on substrate specificity in plant enzymes. Protein science : a publication of the Protein Society\| PubMed ID: 16751602	2006
Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model. European journal of immunology\| PubMed ID: 21182094	2011
Conditional DC depletion does not affect priming of encephalitogenic Th cells in EAE. European journal of immunology\| PubMed ID: 22806332	2012
T cell receptor-Vβ repertoires in lung and blood CD4+ and CD8+ T cells of pulmonary sarcoidosis patients. BMC pulmonary medicine\| PubMed ID: 24656074	2014
Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus. PloS one\| PubMed ID: 25153886	2014

Kerstin M. Ahlgren

Biography

JoVE Journal Publications

Other Publications