A monoclonal antibody to Siglec-8 suppresses non-allergic airway inflammation and inhibits IgE-independent mast cell activation

A monoclonal antibody to Siglec-8 suppresses non-allergic airway inflammation and inhibits IgE-independent mast cell activation.

Full text not available from this repository.
Item Type: Article
Status: Published
Official URL: https://doi.org/10.1038/s41385-020-00336-9
Journal or Publication Title: Mucosal Immunology
Date: 2020
Divisions: UTS Centre for Inflammation
Depositing User: General Admin
Identification Number: 10.1038/s41385-020-00336-9
ISSN: 1933-0219
Date Deposited: 03 Jan 2021 23:56
Abstract:

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.

Creators:
Creators
Email
Schanin, Julia
UNSPECIFIED
Gebremeskel, Simon
UNSPECIFIED
Korver, Wouter
UNSPECIFIED
Falahati, Rustom
UNSPECIFIED
Butuci, Melina
UNSPECIFIED
Haw, Tatt Jhong
UNSPECIFIED
Nair, Prema M.
UNSPECIFIED
Liu, Gang
UNSPECIFIED
Hansbro, Nicole G.
UNSPECIFIED
Hansbro, Philip M.
UNSPECIFIED
Evensen, Erik
UNSPECIFIED
Brock, Emily C.
UNSPECIFIED
Xu, Alan
UNSPECIFIED
Wong, Alan
UNSPECIFIED
Leung, John
UNSPECIFIED
Bebbington, Christopher
UNSPECIFIED
Tomasevic, Nenad
UNSPECIFIED
Youngblood, Bradford A.
UNSPECIFIED
Last Modified: 03 Jan 2021 23:56
URI: https://eprints.centenary.org.au/id/eprint/829

Actions (login required)

View Item View Item