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. Lypd8 may be involved in innate immunity-related pathways against enteric bacterial pathogens [1,2].

Lypd8-deficient mice show rapid colonization of Citrobacter rodentium in the colon, leading to severe colitis with Th17-cell and neutrophil expansion in the lamina propria, indicating its role in early-phase defense against this pathogen [1]. Also, in Lypd8 -/- 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]. These KO mouse models reveal that Lypd8 is essential for preventing bacterial invasion and maintaining a healthy gut environment.

In conclusion, Lypd8 is vital for maintaining gut homeostasis by preventing the attachment and invasion of bacteria, especially flagellated ones, to colonic epithelia. The Lypd8 KO mouse models have been instrumental in highlighting its role in protecting against colitis and other related intestinal diseases, suggesting its potential as a therapeutic target for such conditions [1,2,3].

References:

1. Okumura, Ryu, Kodama, Toshio, Hsu, Chiao-Ching, Iida, Tetsuya, Takeda, Kiyoshi. 2019. Lypd8 inhibits attachment of pathogenic bacteria to colonic epithelia. In Mucosal immunology, 13, 75-85. doi:10.1038/s41385-019-0219-4. https://pubmed.ncbi.nlm.nih.gov/31659301/

2. Okumura, Ryu, Kurakawa, Takashi, Nakano, Takashi, Sano, Koichi, Takeda, Kiyoshi. 2016. Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia. In Nature, 532, 117-21. doi:10.1038/nature17406. https://pubmed.ncbi.nlm.nih.gov/27027293/

3. Hsu, Chiao-Ching, Okumura, Ryu, Motooka, Daisuke, Iida, Tetsuya, Takeda, Kiyoshi. . Alleviation of colonic inflammation by Lypd8 in a mouse model of inflammatory bowel disease. In International immunology, 33, 359-372. doi:10.1093/intimm/dxab012. https://pubmed.ncbi.nlm.nih.gov/33822948/