- Title
- A monoclonal antibody to Siglec-8 suppresses non-allergic airway inflammation and inhibits IgE-independent mast cell activation
- Creator
- Schanin, Julia; Gebremeskel, Simon; Evensen, Erik; Brock, Emily C.; Xu, Alan; Wong, Alan; Leung, John; Bebbington, Christopher; Tomasevic, Nenad; Youngblood, Bradford A.; Korver, Wouter; Falahati, Rustom; Butuci, Melina; Haw, Tatt Jhong; Nair, Prema M.; Liu, Gang; Hansbro, Nicole G.; Hansbro, Philip M.
- Relation
- ARC.DP150102153 http://purl.org/au-research/grants/arc/DP150102153 | NHMRC|1079187 http://purl.org/au-research/grants/nhmrc/1079187 | NHMRC|1023131 http://purl.org/au-research/grants/nhmrc/1023131
- Relation
- Mucosal Immunology Vol. 14, Issue 2, p. 366-376
- Publisher Link
- http://dx.doi.org/10.1038/s41385-020-00336-9
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2021
- Description
- In addition to their well characterized role in mediating IgE-dependent allergic diseases, aberrant accumulation and activation of mast cells (MCs) is associated with many non-allergic inflammatory diseases, whereby their activation is likely triggered by non-IgE stimuli (e.g., IL-33). Siglec-8 is an inhibitory receptor expressed on MCs and eosinophils that has been shown to inhibit IgE-mediated MC responses and reduce allergic inflammation upon ligation with a monoclonal antibody (mAb). Herein, we evaluated the effects of an anti-Siglec-8 mAb (anti-S8) in non-allergic disease models of experimental cigarette-smoke-induced chronic obstructive pulmonary disease and bleomycin-induced lung injury in Siglec-8 transgenic mice. Therapeutic treatment with anti-S8 inhibited MC activation and reduced recruitment of immune cells, airway inflammation, and lung fibrosis. Similarly, using a model of MC- dependent, IL-33-induced inflammation, anti-S8 treatment suppressed neutrophil influx, and cytokine production through MC inhibition. Transcriptomic profiling of MCs further demonstrated anti-S8-mediated downregulation of MC signaling pathways induced by IL-33, including TNF signaling via NF-κB. Collectively, these findings demonstrate that ligating Siglec-8 with an antibody reduces non-allergic inflammation and inhibits IgE-independent MC activation, supporting the evaluation of an anti-Siglec-8 mAb as a therapeutic approach in both allergic and non-allergic inflammatory diseases in which MCs play a role.
- Subject
- monoclonal; cell; cigerette smoking; disease models; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1475648
- Identifier
- uon:49614
- Identifier
- ISSN:1933-0219
- Rights
- © The Author(s) 2020 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/
- Language
- eng
- Full Text
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