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A helminth-derived suppressor of ST2 blocks allergic responses
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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234810/ https://www.ncbi.nlm.nih.gov/pubmed/32420871 http://dx.doi.org/10.7554/eLife.54017 |
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author | Vacca, Francesco Chauché, Caroline Jamwal, Abhishek Hinchy, Elizabeth C Heieis, Graham Webster, Holly Ogunkanbi, Adefunke Sekne, Zala Gregory, William F Wear, Martin Perona-Wright, Georgia Higgins, Matthew K Nys, Josquin A Cohen, E Suzanne McSorley, Henry J |
author_facet | Vacca, Francesco Chauché, Caroline Jamwal, Abhishek Hinchy, Elizabeth C Heieis, Graham Webster, Holly Ogunkanbi, Adefunke Sekne, Zala Gregory, William F Wear, Martin Perona-Wright, Georgia Higgins, Matthew K Nys, Josquin A Cohen, E Suzanne McSorley, Henry J |
author_sort | Vacca, Francesco |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7234810 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-72348102020-05-20 A helminth-derived suppressor of ST2 blocks allergic responses Vacca, Francesco Chauché, Caroline Jamwal, Abhishek Hinchy, Elizabeth C Heieis, Graham Webster, Holly Ogunkanbi, Adefunke Sekne, Zala Gregory, William F Wear, Martin Perona-Wright, Georgia Higgins, Matthew K Nys, Josquin A Cohen, E Suzanne McSorley, Henry J eLife Immunology and Inflammation 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. eLife Sciences Publications, Ltd 2020-05-18 /pmc/articles/PMC7234810/ /pubmed/32420871 http://dx.doi.org/10.7554/eLife.54017 Text en © 2020, Vacca et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Vacca, Francesco Chauché, Caroline Jamwal, Abhishek Hinchy, Elizabeth C Heieis, Graham Webster, Holly Ogunkanbi, Adefunke Sekne, Zala Gregory, William F Wear, Martin Perona-Wright, Georgia Higgins, Matthew K Nys, Josquin A Cohen, E Suzanne McSorley, Henry J A helminth-derived suppressor of ST2 blocks allergic responses |
title | A helminth-derived suppressor of ST2 blocks allergic responses |
title_full | A helminth-derived suppressor of ST2 blocks allergic responses |
title_fullStr | A helminth-derived suppressor of ST2 blocks allergic responses |
title_full_unstemmed | A helminth-derived suppressor of ST2 blocks allergic responses |
title_short | A helminth-derived suppressor of ST2 blocks allergic responses |
title_sort | helminth-derived suppressor of st2 blocks allergic responses |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234810/ https://www.ncbi.nlm.nih.gov/pubmed/32420871 http://dx.doi.org/10.7554/eLife.54017 |
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