AUTHOR=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 TITLE=Potent anti-inflammatory activity of the lectin-like domain of TNF in joints JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1049368 DOI=10.3389/fimmu.2022.1049368 ISSN=1664-3224 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.