Friday, November 9, 2018 - 12:00 to 13:00
CTIR Sir Kenneth and Lady Noreen Murray Seminar Room
Professor Simon Arthur
Dr Henry McSorley
Centre for Inflammation Research, The University of Edinburgh
Dundee Cell Signalling Lecture
Epithelial cytokines such as IL-25, TSLP and IL-33 are potent initiators of type 2 immune responses, and are released rapidly on damage to epithelial barriers. They therefore represent an upstream target for prevention of type 2 immune responses which both cause allergic disease and are responsible for parasite ejection. The intestinal nematode Heligmosomoides polygyrus forms chronic infections in mice, due to its ability to effectively modulate the host immune response. Functional studies of the secreted products of H. polygyrus led us to identify a series of suppressors of the IL-33 pathway, the first of which, the H. polygyrus Alarmin Release Inhibitor (HpARI) binds directly to both IL-33 and to DNA within necrotic cells. This dual functionality of HpARI gives it the unique ability to “tether” IL-33 within necrotic epithelial cells, preventing IL-33 release, and blocking its activity. We have subsequently identified several further modulators of early innate immune responses, with potential for use as therapeutic agents in allergic disease, as helminth vaccine candidates, and as tool compounds for assessing the role of epithelial cytokines in allergy and inflammation.