ABSTRACT: Mogroside V protects Lipopolysaccharides-induced lung inflammation chicken via suppressing inflammation mediated by the Th17 through the gut-lung axis
Project description:Short-chain fatty acids (SCFAs) are the end-products of bacterial fermentation of dietary fibre, and can play a crucial role in regulating immunity and metabolism in the gut and peripheral tissues. Here we show that butyrrate, an SCFA, displayed antiviral effects in chicken respiratory epithelial cells, likely via the regulation of interferon-stimulated genes, particularly OASL. The observed antiviral signaling mechanism would involve HDAC inhibition and Sp1-dependent regulation of the OASL promoter, shedding light on new mechanisms through which the GM regulates poultry mucosal immunity along the gut-lung axis in the chicken.
Project description:Type I IFN-signaling suppresses an excessive IFN-{gamma} response and prevents lung damage and chronic inflammation following Pneumocystis (PC)-infection and clearance in CD4 T cell-competent mice. Type I IFN -signaling in pulmonary CD11c+ DCs and alveolar macrophages may prevent chronic inflammation following PC lung infection and clearance by suppressing an excessive IFN-g-response via the induction of SOCS1.
Project description:Type I IFN-signaling suppresses an excessive IFN-{gamma} response and prevents lung damage and chronic inflammation following Pneumocystis (PC)-infection and clearance in CD4 T cell-competent mice. Type I IFN -signaling in pulmonary CD11c+ DCs and alveolar macrophages may prevent chronic inflammation following PC lung infection and clearance by suppressing an excessive IFN-g-response via the induction of SOCS1. IFNAR-/- and wildtype mice were both Pneumocystis infected via itratracheal instillation. Pulmonary CD11c+ cells were isolated from collagen digested lungs at day 7 and day 14 post infection from both wildtype and IFNAR-/- mice using a magnetic cell sorting technique from Miltenyi with CD11c microbeads. Cells from three individual animals per group were isolated and assessed. Comparison of 2 treatment types at 2 timepoints to determine whether type I IFN signaling is initiated in resident and early recruited pulmonary CD11c+ cells following Pneumocystis lung infection and whether this is relevant to the outcome of the inflammatory response during the initiation of clearance.
Project description:Sepsis-induced acute lung injury (ALI) is a severe clinical condition with a high mortality rate. Tangeretin, widely found in citrus fruits, has been reported to exert antioxidant and anti-inflammatory properties. However, whether Tangeretin protects against sepsis-induced ALI and the potential mechanisms remain unclear.We established ALI model via intraperitoneally injected with 5 mg/kg lipopolysaccharides (LPS) for 12 h. Tangeretin was applied intraperitoneally 30 min before LPS treatment. The lung tissue samples from both the LPS and LPS + TAN groups were subjected to RNA sequencing analysis, conducted by OE Biotech Co., Ltd. (Shanghai, China). We performed differential gene expression analysis using RNA-seq data between LPS and LPS/Tangeretin group.GSEA analysis between LPS and LPS/Tangeretin group showed that IL6_JAK_STAT3_SIGNALING, INFLAMMATORY_RESPONSE, TNFA_SIGNALING_VIA_NFKB were significantly enriched (Fig.3C-E). These results identified the anti-inflammatory effect of Tangeretin against sepsis-induced ALI.
Project description:Background: Recently, Tregs expressing the Th17 characteristic transcription factor RORγt were identified (biTregs). Both, pro- and anti-inflammatory functions have been described and the sum effect of biTreg deficiency in inflammation remains unknown. Furthermore, it is unclear, whether biTregs are specialized for the control of a defined type of immune response, as in particular Th2 or Th17 immunity. Methods: FACsorted CD4+ T-cells from fluorescence reporter mice, containing or lacking biTregs, were transferred into RAG1-/- recipients and the nephrotoxic nephritis model of glomerulonephritis was studied. Interactions of biTregs with various leukocyte populations were assessed by multicolor immunofluorescence. Furthermore, biTregs were compared to other Treg subtypes including suppression assays and RNAseq analyses. Finally, the role of the CCR6/CCL20 axis for biTreg biology was characterized. Results: Lack of endogenous biTregs resulted in aggravation of glomerulonephritis, demonstrating net immunosuppressive functions. However, contrary to our hypothesis, biTreg deficiency did not result in selectively overshooting Th2 or Th17 responses. Comprehensive analysis instead revealed a unique functional and transcriptional biTreg profile, including high production of IL-10 and dependency on IL-6R, cMAF and IKZF3 activation. Interestingly, we found that expression of the chemokine receptor CCR6 marked a particularly activated biTreg subset, whose absence significantly worsened glomerulonephritis. Unexpectedly, we found that signaling via the CCR6/CCL20 axis mediates biTreg expansion, rather than trafficking. Our data indicate net immunosuppressive effects of endogenous biTregs, with no preference for regulation of Th2 or Th17 responses. Surprisingly, signaling via the Conclusion: CCR6/CCL20 axis was integral for biTreg expansion and activation, which offers novel therapeutic options.