IL-33/ST2 signalling and crosstalk with FcεRI and TLR4 is targeted by the parasitic worm product, ES-62

Dimity H. Ball, Lamyaa Al-Riyami, William Harnett, Margaret M. Harnett

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12 Citations (Scopus)
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ES-62 is a secreted parasitic worm-derived immunomodulator that exhibits therapeutic potential in allergy by downregulating aberrant MyD88 signalling to normalise the inflammatory phenotype and mast cell responses. IL-33 plays an important role in driving mast cell responses and promoting type-2 allergic inflammation, particularly with respect to asthma, via MyD88-integrated crosstalk amongst the IL-33 receptor (ST2), TLR4 and FcϵRI. We have now investigated whether ES-62 targets this pathogenic network by subverting ST2-signalling, specifically by characterising how the functional outcomes of crosstalk amongst ST2, TLR4 and FcϵRI are modulated by the worm product in wild type and ST2-deficient mast cells. This analysis showed that whilst ES-62 inhibits IL-33/ST2 signalling, the precise functional modulation observed varies with receptor usage and/or mast cell phenotype. Thus, whilst ES-62's harnessing of the capacity of ST2 to sequester MyD88 appears sufficient to mediate its inhibitory effects in peritoneal-derived serosal mast cells, downregulation of MyD88 expression appears to be required to dampen the higher levels of cytokine production typically released by bone marrow-derived mucosal mast cells.

Original languageEnglish
Article number4497
Pages (from-to)1-15
Number of pages15
JournalScientific Reports
Issue number1
Publication statusPublished - 14 Mar 2018


  • inflammation
  • mechanisms of disease

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