Over the past years, it has become clear that Tumor Necrosis Factor (TNF) is a key player in the pathogenesis of spondyloarthritis, a disease leading to joint inflammation of axial skeleton and peripheral joints, but the mechanisms by which this occurs are only partially known. Particularly, the cellular targets sufficient to mediate the articular and extra-articular manifestations (gut and skin inflammation) of spondyloarthritis remained to be defined, as well as the cellular constituents capable of modulating this TNF driven inflammation. Recently, mesenchymal cells were found to be principle targets for TNF in a mouse model of spondyloarthritis, characterized by enhanced TNF mRNA stability, resulting in Crohn’s like ileitis as well as peripheral arthritis. Hence, TNF-R1 expression on mesenchymal cells was sufficient to mediate combined gut and joint pathologies in this model of murine spondyloarthritis. Strikingly, in the earliest phase of disease, inflammation was found to be restricted to enthesial sites. Using a variety of strategies we found that mechanical strain is an important contributor to the disease pathogenesis in this model. Overall, the data suggest an essential role of mechanotransduction in the onset of spondyloarthritides.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.