Alleviation of colonic inflammation by Lypd8 in a mouse model of inflammatory bowel disease

• Published in: International immunology Vol. 33; no. 7; pp. 359 - 372
• Main Authors: Hsu, Chiao-Ching, Okumura, Ryu, Motooka, Daisuke, Sasaki, Reo, Nakamura, Shota, Iida, Tetsuya, Takeda, Kiyoshi
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 01-07-2021
• Subjects: Animals; Colitis - chemically induced; Colitis - metabolism; Colon - metabolism; Dextran Sulfate - pharmacology; Diet, High-Fat; Disease Models, Animal; Dysbiosis - chemically induced; Dysbiosis - metabolism; Female; Gastrointestinal Microbiome - physiology; GPI-Linked Proteins - metabolism; Humans; Inflammation - chemically induced; Inflammation - metabolism; Inflammatory Bowel Diseases - chemically induced; Inflammatory Bowel Diseases - metabolism; Intestinal Mucosa - metabolism; Mice; Mice, Inbred C57BL; Lypd8; inflammatory bowel diseases; mucosal barrier; high-fat diet
• ISSN: 1460-2377; 1460-2377
• DOI: 10.1093/intimm/dxab012

Abstract
Dysfunction of the intestinal mucosal barrier causes inflammatory bowel diseases (IBDs). Indeed, mucosal barrier impairment in the gut of IBD patients results from decreased expression of barrier molecules. Ly6/Plaur domain containing 8 (Lypd8) segregates microbiota from the colonic epithelial layer. In this study, we found that Lypd8−/− mice, in which flagellated bacteria invaded the mucosal surface of the colon, developed spontaneous colitis when dysbiosis was induced by a high-fat diet (HFD). On the basis of this finding, we assessed whether the application of human LYPD8 (hLYPD8) protein exhibiting the glycan-dependent inhibition of bacterial motility is effective in a colitis model. Oral and anal treatments with hLYPD8 protein ameliorate dextran sulfate sodium-induced colitis and HFD-induced colitis in Lypd8−/− mice. These results indicate a therapeutic potential of hLYPD8 protein supplementation for IBD.
Lypd8 mediates effective protection from colitis