IL-33/ST2 signalling and crosstalk with FcεRI and TLR4 is targeted by the parasitic worm product, ES-62
Ball, Dimity H. and Al-Riyami, Lamyaa and Harnett, William and Harnett, Margaret M. (2018) IL-33/ST2 signalling and crosstalk with FcεRI and TLR4 is targeted by the parasitic worm product, ES-62. Scientific Reports, 8 (1). pp. 1-15. 4497. ISSN 2045-2322
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Abstract
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.
Creators(s): |
Ball, Dimity H., Al-Riyami, Lamyaa, Harnett, William ![]() | Item type: | Article |
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ID code: | 63840 |
Keywords: | inflammation, mechanisms of disease, Therapeutics. Pharmacology, Pharmacology (medical) |
Subjects: | Medicine > Therapeutics. Pharmacology |
Department: | Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences |
Depositing user: | Pure Administrator |
Date deposited: | 24 Apr 2018 14:20 |
Last modified: | 21 Jan 2021 10:01 |
Related URLs: | |
URI: | https://strathprints.strath.ac.uk/id/eprint/63840 |
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