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We also found that levels of IFN-γ and IL-17 released in Peyer’s patch cells were significantly increased in EV-A71, after it was combined with PS-G. We further demonstrated that both CD4+ and CD8+ T cells were able to generate IFN-γ and IL-17 in the spleen. An easy-accessed model of hybrid hSCARB2+/+/stat-1-/- mice was used for EV-A71 infection and pathogenesis. We infected the mouse model with EV-A71, which was premixed with mouse sera immunized with the EV-A71 vaccine with or without PS-G. Indeed, in the EV-A71 + PS-G group, the levels of VP1-specific RNA sequences in the brain, spinal cord, and muscle decreased significantly. Finally, hSCARB2-Tg mice immunized via the intranasal route with the PS-G-adjuvanted EV-A71 vaccine resisted a subsequent lethal oral EV-A71 challenge. Taken together, these results demonstrated that PS-G could potentially be used as an adjuvant for the EV-A71 mucosal vaccine.Thin melanomas are tumors less than 1 mm thick according to Breslow classification. Their prognosis is in most cases excellent. However, a small subset of these tumors relapses. These clinical findings emphasize the need of novel prognostic biomarkers to identify this subset of tumors. click here Characterization of tumor immune microenvironment (TIME) is currently investigated as a prognostic and predictive biomarker for cancer immunotherapy in several solid tumors including melanoma. Here, taking into account the limited availability of tumor tissues, by characterizing some of the characteristics of TIME such as number of infiltrating lymphocytes, HLA class I antigen and PD-L1 expression, we show that number of infiltrating CD8+ and FOXP3+ T cells as well as CD8+/FOXP3+ T cell ratio can represent a useful prognostic biomarker in thin melanoma. Although further investigations in a larger patient cohort are needed, these findings have potential clinical significance since they can be used to define subgroups of thin melanoma patients who have a worse prognosis and might need different treatment modalities.Vitamin A deficiency (A-) increases morbidity and mortality to gastrointestinal (GI) infection. Blocking retinoid signaling (dominant negative retinoic acid receptor, dnRAR) in intestinal epithelial cells (IEC, IECdnRAR) had no effect on vitamin A absorption, the expression of tight junction proteins or the integrity of the barrier. Immune cells in the gut were present in normal frequencies in the IECdnRAR mice, with the exception of the T cell receptor (TCR)αβ+/CD8αα cells, which were significantly lower than in wildtype littermates. Challenging the IECdnRAR mice with dextran sodium sulfate to induce colitis or Citrobacter rodentium infection resulted in similar disease to wildtype littermates. Feeding mice vitamin A deficient diets reduced vitamin A status and the A- IECdnRAR mice developed more severe colitis and C. rodentium infection. In particular, retinoid signaling in the IEC was crucial for the A- host to survive early infection following C. rodentium. Treating A- mice with retinoic acid (RA) beginning on the day of infection protects most mice from early lethality. However, RA treatment of the A- IECdnRAR mice was ineffective for preventing lethality following C. rodentium infection. Retionid signaling in IEC is critical, especially when there are reduced levels of dietary vitamin A. IEC are direct targets of vitamin A for mounting early defense against infection.In addition to their antibiotic activities, azithromycin (AZM) exhibits anti-inflammatory effects in various respiratory diseases. One of the potent anti-inflammatory mechanisms is through inhibition of CD4+ helper T (Th) cell effector function. However, their impact on specific Th subset is obscure. Herein, we demonstrate the cellular basis of phenotypic and functional alterations associated with Th subsets following AZM treatment in vitro. Using well-characterized Th subset specific chemokine receptors, we report significant suppression of T cell receptor (TCR)-stimulated hyperactivated CCR4+CXCR3+ (Th0) expansion compared to CCR4-CXCR3+ (Th1-like) and CCR4+CXCR3- (Th2-like) cells. Interestingly, this effect was associated with diminished cell proliferation. Furthermore, AZM significantly inhibited the inflammatory cytokines IFN-γ and IL-4 production, CCR4 and CXCR3 receptor expression, and viability of Th0, Th1-like, and Th2-like subsets. Our findings suggest that AZM differentially affects TCR-activated Th subsets phenotype and function, and CCR4 and CXCR3 downregulation and suppressed Th0 subset expansion could potentially influence their trafficking and differentiation into cytokine-producing effector cells.Leonurine, an active alkaloid extracted from Herba leonuri, is reported to have potent anti-inflammatory activity against rheumatoid arthritis (RA). However, the molecular mechanism of action of leonurine in RA remains poorly understood. In this study, we detected 3,425 mRNAs differentially expressed between CD4+ T cells of RA patients and those of healthy individuals using microarray raw data mining. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes including T-helper (Th)-17 cell development, and was thus selected for functional verification. In a naïve CD4+ T cell differentiation assay, we found that TAZ overexpression was associated with impaired balance between T regulatory (Treg) and Th17 cells in vitro. TAZ overexpression increased the levels of the pro-inflammatory cytokines interleukin (IL)-17, IL-1β, and tumor necrosis factor (TNF)-α and decreased that of the anti-inflammatory cytokine IL-10. Leonurine treatment had a direct recovery effect on the impaired balance and reduced the expression of TAZ and led to normalization of IL-17, IL-1β, and TNF-α and IL-10. Furthermore, IL-6 was found to promote the expression of TAZ and receptor activator of nuclear factor kappa-B ligand (RANKL), and RANK. Leonurine significantly inhibited TAZ-mediated expression of RANKL, and RANK and IL-6 in synovial fibroblasts. We conclude that the therapeutic effect of leonurine was through suppression of TAZ led to restoration of Treg/Th17 balance and suppression of synovial fibroblast action.