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A helminth-derived suppressor of ST2 blocks allergic responses

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Original languageEnglish
Article numbere54017
JournaleLIFE
Volume9
DOIs
Publication statusPublished - 18 May 2020

Abstract

t The IL-33-ST2 pathway is an important initiator of type 2 immune responses. We
previously characterised the HpARI protein secreted by the model intestinal nematode
Heligmosomoides polygyrus, which binds and blocks IL-33. Here, we identify H. polygyrus Binds
Alarmin Receptor and Inhibits (HpBARI) and HpBARI_Hom2, both of which consist of complement
control protein (CCP) domains, similarly to the immunomodulatory HpARI and Hp-TGM proteins.
HpBARI binds murine ST2, inhibiting cell surface detection of ST2, preventing IL-33-ST2
interactions, and inhibiting IL-33 responses in vitro and in an in vivo mouse model of asthma. In H.
polygyrus infection, ST2 detection is abrogated in the peritoneal cavity and lung, consistent with
systemic effects of HpBARI. HpBARI_Hom2 also binds human ST2 with high affinity, and effectively
blocks human PBMC responses to IL-33. Thus, we show that H. polygyrus blocks the IL-33 pathway
via both HpARI which blocks the cytokine, and also HpBARI which blocks the receptor.

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