As parasitic helminths have coevolved with us, they have developed sophisticated techniques in order to persist within their host environment. One of the mechanisms they have utilised to achieve this is through the release of soluble products (including proteins) which directly bind to, and modulate, host immune mediators such as cytokines. My group’s work focuses on the earliest events in immune response initiation, and how parasite proteins can modulate these. The murine intestinal nematode Heligmosomoides polygyrus suppresses type 2 immune responses, and infection with this parasite, or administration of its products, suppresses allergic inflammation in mouse models of asthma, through suppression of the release of the pro-allergic epithelial cytokine IL-33. The H. polygyrus Alarmin Release Inhibitor (HpARI) was identified through proteomic analysis, and is a potent inhibitor of IL-33 responses. Binding studies showed that HpARI binds to IL-33 with high affinity, blocking downstream responses, and that HpARI also binds to nuclear DNA, resulting in tethering of IL-33 within damaged epithelial cells, preventing its release. Further analysis of H. polygyrus secretions has led to the identification of other immunomodulatory proteins, including a suppressor of the IL-33 receptor, and of IL-25 responses - and further immune targets are currently being investigated. Despite disparate functions, all of the immunomodulatory proteins that we have identified belong to a structurally-related family which have never before been investigated in parasitic worms, therefore this family represents a focus of my future research. The identification and characterisation of these immunomodulators will not only elucidates the fascinating interaction between parasites and their hosts, but also has the potential for development of new therapeutic agents in allergic disease, as helminth vaccine candidates, and as tool compounds for assessing the role of epithelial cytokines in allergy and inflammation.