PhD STUDENT, UNIVERSITY OF TECHNOLOGY
Autophagy process is critical in presenting environmental allergens to inflammatory cells.
Thunderstorms have been recognized worldwide as one of the major precipitant of environmental change induced asthma. Thunderstorm causes unusually high pollen in the air triggering severe asthma attacks.. Recent understanding of Autophagy and its role in immunology has opened avenue for its research in asthma drug development. More specifically, autophagy process regulation is noticed in nuclear and cytoplasmic antigen delivery to cell surface (MHC class II molecules) for presentation to inflammatory cells (CD4+ T cells). My project aimed to explore the role of autophagy in severe asthma and its therapeutic potential using autophagy inhibitor.
Abstract: This study illustrates the potential of using emergency department attendance data, routinely accessed as part of a national syndromic surveillance system, to monitor the impact of thunderstorm asthma.The Emergency Department Syndromic Surveillance System (EDSSS) routinely monitors anonymised attendance data on a daily basis across a sentinel network of 35 emergency departments. Attendance data for asthma, wheeze and difficulty breathing are analysed on a daily basis.A statistically significant spike in asthma attendances in two EDSSS emergency departments in London was detected on 23 July 2013, coinciding with a series of large violent thunderstorms across southern England. There was also an increase in the reported severity of these attendances.This preliminary report illustrates the potential of the EDSSS to monitor the impact of thunderstorms on emergency department asthma attendances. Further work will focus on how this system can be used to quantify the impact on emergency departments, thus potentially improving resource planning and also adding to the thunderstorm asthma evidence-base.
Pub.: 09 Oct '13, Pinned: 27 Jul '17
Abstract: Antibody responses to citrullinated self-proteins are found in autoimmunities, particularly in rheumatoid arthritis, where they serve as a diagnostic indicator. We show here that processing of the protein hen egg-white lysozyme (HEL) resulted in citrullination of peptides presented on class II MHC molecules by antigen-presenting cells. The presentation of the citrullinated peptides but not of the unmodified peptides was associated with autophagy. Dendritic cells (DCs), macrophages, and thymic DCs presented citrullinated peptides constitutively. Their treatment with 3-methyladenine (3MA) blocked presentation of citrullinated HEL peptides, but presentation of unmodified peptides was not affected. Presentation of citrullinated peptides was not detected on B cells or B lymphoma cells under normal culture conditions. In B cells, engagement of the B cell antigen receptor was required for presentation of the citrullinated peptides, also inhibited by 3MA. B lymphoma-expressing HEL cells presented citrullinated peptides only after brief serum starvation. This presentation was reduced by 3MA or by reduction in Atg5 expression. Presentation of the unmodified peptides was not changed. The findings indicate a linkage between autophagy and autoreactivity through the generation of this neo-epitope.
Pub.: 14 Dec '11, Pinned: 27 Jul '17
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