An inhibitory immunoreceptor Allergin-1 regulates the intestinal dysbiosis and barrier function in mice

• Published in: International immunology Vol. 36; no. 7; p. 365
• Main Authors: Lin, Yu-Hsien, Tahara-Hanaoka, Satoko, Obana, Nozomu, Fukuda, Shinji, Shibuya, Akira
• Format: Journal Article
• Language: English
• Published: England 08.06.2024
• Subjects: Animals; Colitis - immunology; Colitis - microbiology; Dextran Sulfate; Dysbiosis - immunology; Gastrointestinal Microbiome - immunology; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neomycin - pharmacology; Permeability; Receptors, Immunologic - genetics; Receptors, Immunologic - immunology; Receptors, Immunologic - metabolism; DSS-induced colitis; 16S rRNA gene sequencing; Bifidobacterium pseudolongum
• ISSN: 1460-2377; 1460-2377
• DOI: 10.1093/intimm/dxae010

The intestinal barrier consists of mucosal, epithelial, and immunological barriers and serves as a dynamic interface between the host and its environment. Disruption of the intestinal barrier integrity is a leading cause of various gastrointestinal diseases, such as inflammatory bowel disease. The homeostasis of the intestinal barrier is tightly regulated by crosstalk between gut microbes and the immune system; however, the implication of the immune system on the imbalance of gut microbes that disrupts barrier integrity remains to be fully elucidated. An inhibitory immunoglobulin-like receptor, Allergin-1, is expressed on mast cells and dendritic cells and inhibits Toll-like receptor (TLR)-2 and TLR-4 signaling in these cells. Since TLRs are major sensors of microbiota and are involved in local epithelial homeostasis, we investigated the role of Allergin-1 in maintaining intestinal homeostasis. Allergin-1-deficient (Milr1-/-) mice exhibited more severe dextran sulfate sodium (DSS)-induced colitis than did wild-type (WT) mice. Milr1-/- mice showed an enhanced intestinal permeability compared with WT mice even before DSS administration. Treatment of Milr1-/- mice with neomycin, but not ampicillin, restored intestinal barrier integrity. The 16S rRNA gene sequencing analysis demonstrated that Bifidobacterium pseudolongum was the dominant bacterium in Milr1-/- mice after treatment with ampicillin. Although the transfer of B. pseudolongum to germ-free WT mice had no effect on intestinal permeability, its transfer into ampicillin-treated WT mice enhanced intestinal permeability. These results demonstrated that Allergin-1 deficiency enhanced intestinal dysbiosis with expanded B. pseudolongum, which contributes to intestinal barrier dysfunction in collaboration with neomycin-sensitive and ampicillin-resistant microbiota.