Summary

All body surfaces and cavities are lined by layers of epithelial cells, which are connected by cell-cell junctions. These junctions serve three main purposes: adhesion, to maintain tissue integrity; creation of a barrier, to control the passage of ions, water, molecules, cells, and pathogens across epithelial layers; and signaling, to receive and transmit cues that affect cell behavior and tissue function. The barrier function is crucial to maintaining tissue homeostasis. Breaking or even slightly perturbing epithelial barriers can lead to serious pathological consequences, including infection and inflammation (1–3). The intestinal epithelial barrier is constantly being challenged by the gut microbiome, and is leaky in patients with inflammatory bowel disease (IBD) (1, 3, 4). Three studies now characterize how gut epithelial barrier dysfunction is involved in IBD, autoimmune disease, and systemic infection, respectively. On page 1161 of this issue, Mohanan et al. (5) describe how inactivation of the IBD susceptibility gene, C1orf106 (chromosome 1 open reading frame 106), leads to decreased intestinal barrier function, thereby promoting intestinal inflammation and thus IBD. Also, on page 1156 of this issue, Manfredo Vieira et al. (6) show how pathogenic bacteria can induce intestinal barrier defects and translocate to lymph nodes and liver, triggering systemic autoimmune disease, such as systemic lupus erythematosus (SLE). Additionally, Thaiss et al. (7) report that hyperglycemia (high blood glucose concentration), which is common in people with obesity, diabetes, and other metabolic syndromes, disrupts the intestinal barrier, leading to intestinal inflammation and systemic infection complications.