Ly6/Plaur domain-containing 8 (Lypd8), a highly glycosylated glycosylphosphatidylinositol-anchored protein, is selectively expressed on colonic enterocytes. It plays a crucial role in maintaining gut homeostasis by segregating commensal microbes from the intestinal epithelia. It may be involved in innate immunity-related pathways to protect against enteric bacterial pathogens [1,2].

In Lypd8-deficient mice, there are significant consequences. For instance, they show rapid Citrobacter rodentium colonization in the colon, leading to severe colitis with Th17-cell and neutrophil expansion in the lamina propria, indicating Lypd8's role in early-phase defense against this pathogen [1]. Also, in these mice, flagellated bacteria invade the mucosal surface of the colon, and when dysbiosis is induced by a high-fat diet, they develop spontaneous colitis [3]. Additionally, the absence of Lypd8 leads to bacteria being present in the inner mucus layer, with many flagellated bacteria invading epithelia, and these mice are highly sensitive to dextran sulfate sodium (DSS)-induced intestinal inflammation [2].

In conclusion, Lypd8 is essential for maintaining the segregation of microbiota from colonic epithelia, thus protecting against intestinal inflammation and infections. The use of Lypd8 knockout mouse models has been instrumental in revealing its role in conditions such as colitis and defense against enteric bacterial pathogens, highlighting its potential as a therapeutic target for related diseases [1,2,3].