Fig. 1

Normal intestinal barrier and the “leaky gut” of arthritis. The normal intestinal barrier is a physical barrier comprised of epithelial cells sealed by interepithelial tight junctions. In animal models, the onset of arthritis is preceded by dysbiosis and disruption of intestinal barrier integrity (“leaky” gut) due to secretion of zonulin by intestinal epithelial cells, destabilization of tight junctions, and necroptosis of epithelial cells. Inhibitors of necroptosis and antagonists of zonulin restore the integrity of intestinal barrier and ameliorate arthritis. HIF 1a, hypoxia-inducible factor 1 alpha; RIPK3, receptor-interacting protein kinase 3. This figure was created with BioRender.com