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- W4313368475 abstract "Abstract The maintenance of intestinal homeostasis depends on a complex interaction between microbiota, intestinal epithelial barrier, and the immune system. Alteration in of one of these components could lead to the development of inflammatory bowel diseases (IBD). Norovirus infection of mice with a mutation in the Crohn’s disease susceptibility gene Atg16L1 induces intestinal inflammation. Moreover, persistent norovirus infection leads to intestinal virus-specific CD8+ T cells responses. However, the role of the enteric virome in IBD is still poorly understood. Toll-like receptor 7 (TLR7) recognizes single-stranded RNA viruses. Here, we investigate the role of TLR7 in intestinal homeostasis and inflammation. At steady state, Tlr7−/− mice have an approx. 10-fold increase in small and large intestinal lamina propria (LP) granzyme B+ tissue-resident memory (Trm) CD8+ T cells compared to WT mice (WT: 5.5, Tlr7−/−: 59.5 %, p < 0.005), reminiscent of persistent norovirus infection. Furthermore, Tlr7−/− mice were more susceptible to dextran sulfate sodium (DSS) colitis with more severe inflammation (Histoscore: WT: 7.6, Tlr7−/−: 12.7, p < 0.005), increased disease activity index (WT: 5.5, Tlr7−/−: 7.4, p < 0.05), and increased secretion of IFNg (WT: 5.2, Tlr7−/−: 24.2 ng/ml, p < 0.005) and TNFα (WT: 108.6, Tlr7−/−: 191.8 pg/ml, p < 0.05). Increased colonic inflammation was associated with increased LP Trm CD8+ T cells (WT: 3.9, Tlr7−/−: 42.0 %, p < 0.005). Our data shows that TLR7-deficiency promotes the development of LP Trm CD8+ T cells and increases susceptibility to DSS colitis. In conclusion, TLR7 plays an important role in maintaining immune response to intestinal viruses and protects against development of colitis." @default.
- W4313368475 created "2023-01-06" @default.
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- W4313368475 date "2020-05-01" @default.
- W4313368475 modified "2023-09-27" @default.
- W4313368475 title "Toll-like receptor 7 protects against intestinal inflammation and restricts the development of tissue-resident memory CD8+ T cells" @default.
- W4313368475 doi "https://doi.org/10.4049/jimmunol.204.supp.233.16" @default.
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