Potent anti-inflammatory activity of the lectin-like domain of TNF in joints

Language
en
Document Type
Article
Issue Date
2022-11-14
First published
2022-10-31
Issue Year
2022
Authors
Pinto, Ana Carolina Matias Dinelly
Nunes, Rodolfo de Melo
Nogueira, Igor Albuquerque
Fischer, Bernhard
Lucas, Rudolf
Girão-Carmona, Virgínia Claudia Carneiro
de Oliveira, Vivian Louise Soares
Amaral, Flavio Almeida
Schett, Georg
Rocha, Francisco Airton Castro
Editor
Publisher
Frontiers Media S.A.
Abstract

In view of the crucial role of tumor necrosis factor (TNF) in joint destruction, TNF inhibitors, including neutralizing anti-TNF antibodies and soluble TNF receptor constructs, are commonly used therapeutics for the treatment of arthropathies like rheumatoid arthritis (RA). However, not all patients achieve remission; moreover, there is a risk of increased susceptibility to infection with these agents. Spatially distinct from its receptor binding sites, TNF harbors a lectin-like domain, which exerts unique functions that can be mimicked by the 17 residue solnatide peptide. This domain binds to specific oligosaccharides such as N′N′-diacetylchitobiose and directly target the α subunit of the epithelial sodium channel. Solnatide was shown to have anti-inflammatory actions in acute lung injury and glomerulonephritis models. In this study, we evaluated whether the lectin-like domain of TNF can mitigate the development of immune-mediated arthritis in mice. In an antigen-induced arthritis model, solnatide reduced cell influx and release of pro-inflammatory mediators into the joints, associated with reduction in edema and tissue damage, as compared to controls indicating that TNF has anti-inflammatory effects in an acute model of joint inflammation via its lectin-like domain.

Journal Title
Frontiers in Immunology
Volume
13
Citation
Zugehörige ORCIDs