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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

LanguageEnglish
Article number4497
Pages1-15
Number of pages15
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 14 Mar 2018

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Helminths
Mast Cells
Down-Regulation
Phenotype
Toll-Like Receptor 4
Immunologic Factors
Interleukin-33
Hypersensitivity
Asthma
Bone Marrow
Cytokines
Inflammation

Keywords

  • inflammation
  • mechanisms of disease

Cite this

Ball, Dimity H. ; Al-Riyami, Lamyaa ; Harnett, William ; Harnett, Margaret M. / IL-33/ST2 signalling and crosstalk with FcεRI and TLR4 is targeted by the parasitic worm product, ES-62. In: Scientific Reports. 2018 ; Vol. 8, No. 1. pp. 1-15.
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IL-33/ST2 signalling and crosstalk with FcεRI and TLR4 is targeted by the parasitic worm product, ES-62. / Ball, Dimity H.; Al-Riyami, Lamyaa; Harnett, William; Harnett, Margaret M.

In: Scientific Reports, Vol. 8, No. 1, 4497, 14.03.2018, p. 1-15.

Research output: Contribution to journalArticle

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