Gut signals are sent through the basement membrane and epithelial cells receive signals through HVEM proteins on their surface that stimulate synthesis of basement membrane proteins. Without HVEM, the epithelial cells couldn't perform because they produced less collagen and other structural components needed to maintain a healthy basement membrane, the La Jolla Institute for Immunology researchers found (Science Immunology, July 29, 2022).

Using a mouse model and intra-vital imaging RNA, the California researchers found that removing HVEM expression was a major blow to gut health -- patrolling T cells could not survive as well, and they didn't move as much. When challenged with Salmonella typhimurium, the T cells allowed the infection to take over the intestines and spread to the liver and spleen. HVEM from epithelial cells laid the groundwork for T cells to guard the gut and communicated with the T cells indirectly through the basement membrane.

Next up, the researchers are interested in investigating the role of HVEM in maintaining a healthy population of gut microbes because there are signs that a lack of HVEM can sway the composition of the gut microbiome even in the absence of pathogenic bacteria.