Day 2 :
Keynote Forum
Kathleen B Schwarz
Johns Hopkins University School of Medicine, USA
Keynote: Hypothesis testing: A role for inflammasome activation in pediatric autoimmune hepatitis
Time : 10:00-10:30
Biography:
Kathleen B Schwarz was graduated from Washington University School of Medicine, USA. She is a Professor of Pediatrics at the Johns Hopkins University School of Medicine where she is the Director of the Pediatric Liver Center. She is the President of the Federation for International Societies of Pediatric Gastroenterology, Hepatology and Nutrition. She has published more than 165 papers in peer-reviewed journals.
Abstract:
Introduction: An infectious trigger in a genetically susceptible host has been proposed as etiopathogenic in autoimmune hepatitis (AIH). Often formalin-fixed paraffin-embedded liver biopsies (FFPE) are the only hepatic tissues available for pathogenetic investigations but retrieval of mRNA from small biopsies is problematic. Our overall goal was to develop methods to obtain high quality mRNA from FFPE liver biopsies in order to perform unbiased high throughput sequencing of transcriptomes.rnrnMethods: 45 FFPE liver biopsies, 25 from AIH type 1 patients’ and 21 from controls were used to generate RNA libraries and analyzed using RNAseq. Total RNA was extracted from two cored tissue samples, cDNA libraries were constructed using the Illumina TruSeq Stranded Total RNA Sample Preparation Kit with Ribo-Zero to remove cytoplasmic and mitrochondrial rRNA and indexed paired-end sequencing was performed on an Illumina HiSeq2000 with 90 million paired reads per sample.rnrnResults: There was up-regulation in AIH patients; vs. controls of a number of intrahepatic genes; among these were genes related to B cell development and several consistent with activation of the NLRPEi inflammasome. The approach to further investigating a role of NLRPi inflammasome activation in AIH will be discussed including PCR and immunohistochemistry of liver biopsies and serum ELISA assays for inflammasome components as well as PBMC assays.rnrnConclusions: Possible therapeutic implications, including monoclonal antibodies against inflammasome components as well as anakinra (anti IL-1), beta hydroxybutyrate and the sulfonyl urea MCC950 which block NLRPEi will be discussed.rn
Keynote Forum
Yaffa Mizrachi Nebenzahl
Ben Gurion University of the Negev, Israel
Keynote: Natural killer receptor 1 dampens the development of allergic eosinophilic airway inflammation
Time : 10:30-11:00
Biography:
Yaffa Mizrachi Nebenzahl has completed her PhD at The Weizmann Institute, Israel in 1985. She is the Head of the Molecular Microbiology Laboratory in The Shraga Segal Department of Microbiology, Immunology and Genetics at the Faculty of Health Sciences in Ben Gurion University of the Negev, Israel.
Abstract:
The function of NCR1 was studied in a model of experimental asthma, classified as a type 1 hypersensitivity reaction, in mice. IgE levels were significantly increased in the serum of OVA immunized NCR1 deficient (NCR1gfp/gfp) mice in comparison to OVA immunized wild type (NCR1+/+) and adjuvant immunized mice. Histological analysis of OVA immunized NCR1gfp/gfp mice revealed no preservation of the lung structure and overwhelming peribronchial and perivascular granulocytes together with mononuclear cells infiltration. OVA immunized NCR+/+ mice demonstrated preserved lung structure and peribronchial and perivascular immune cell infiltration to a lower extent than that in NCR1gfp/gfp mice. Adjuvant immunized mice demonstrated lung structure preservation and no immune cell infiltration. OVA immunization caused an increase in PAS production independently of NCR1 presence. Bronchoalveolar lavage (BAL) revealed NCR1 dependent decreased percentages of eosinophils and increased percentages of lymphocytes and macrophages following OVA immunization. In the OVA immunized NCR1gfp/gfp mice the protein levels of eosinophils’ (CCL24) and Th2 CD4+ T-cells’ chemo attractants (CCL17 and CCL24) in the BAL are increased in comparison with OVA immunized NCR+/+ mice. In the presence of NCR1, OVA immunization caused an increase in NK cells numbers and NCR1 ligand expression on CD11c+GR1+ cells but a decreased NCR1 mRNA expression in the BAL. OVA immunization resulted in significantly increased IL-13, IL-4 and CCL17mRNA expression in NCR1+/+ and NCR1gfp/gfp mice. IL-17 and TNFα expression increased only in OVA-immunized NCR1+/+ mice. IL-6 mRNA increased only in OVA immunized NCR1gfp/gfp mice. Collectively, it is demonstrated that NCR1 dampens allergic eosinophilic airway inflammation.
- Track 8: Infectious Diseases and Immune System
Track 9: Reproductive Immunology
Track 10: Auto Immunity
Track 13: Diagnostic Immunology
Track 14:Allergy and Therapathies
Track 15:Technological Innovations in Immunology