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- Title
An inhibitory immunoreceptor Allergin-1 regulates the intestinal dysbiosis and barrier function in mice.
- Authors
Lin, Yu-Hsien; Tahara-Hanaoka, Satoko; Obana, Nozomu; Fukuda, Shinji; Shibuya, Akira
- Abstract
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.
- Subjects
INTESTINAL barrier function; INFLAMMATORY bowel diseases; MICE; DEXTRAN sulfate; DENDRITIC cells
- Publication
International Immunology, 2024, Vol 36, Issue 7, p365
- ISSN
0953-8178
- Publication type
Article
- DOI
10.1093/intimm/dxae010