IL-33 Protects Mice against DSS-Induced Chronic Colitis by Increasing Both Regulatory B Cell and Regulatory T Cell Responses as Well as Decreasing Th17 Cell Response.

BACKGROUND: Previously, we have reported that IL-33 functioned as a protective modulator in dextran sulfate sodium- (DSS-) induced chronic colitis by suppressing Th17 cell response in colon lamina propria and IL-33 induced both regulatory B cells (Bregs) and regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) of mice with DSS-induced acute colitis. Moreover, we speculated that IL-33 would promote the Treg or Breg responses leading to the attenuation of DSS-induced chronic colitis. So, we investigated the role of IL-33 on Bregs and Tregs in the MLN of DSS-induced chronic colitis mice. METHODS: IL-33 was administered by intraperitoneal injection to mice with DSS-induced chronic colitis. Clinical symptoms, colon length, and histological changes were determined. The production of cytokines was measured by ELISA. The T and B cell subsets were measured by flow cytometry. The expression of mRNA of transcription factors was measured by quantitative real-time PCR. RESULTS: We show that IL-33 treatment increases both Breg and Treg responses in the MLN of mice with DSS-induced chronic colitis. Moreover, IL-33 treatment also decreases Th17 cell response in the MLN of mice with DSS-induced chronic colitis. CONCLUSION: Our data provide clear evidence that IL-33 plays a protective role in DSS-induced chronic colitis, which is closely related to increasing Breg and Treg responses in the MLN of mice as well as suppressing Th17 cell responses.

Sodium selenite ameliorates dextran sulfate sodium-induced chronic colitis in mice by decreasing Th1, Th17, and γδT and increasing CD4(+)CD25(+) regulatory T-cell responses.

AIM: To assess the effect of sodium selenite on the severity of dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. METHODS: Mice were randomly divided into four groups (n = 10/group): normal group, selenium (Se) group, chronic colitis group, and Se + chronic colitis group. The mice were sacrificed on day 26. Survival rates, clinical symptoms, colon length, and histological changes were determined. The percentages and absolute numbers of immune system cells in the lamina propria lymphocytes (LPL) of the colon, the expression of mRNA in colon tissue, and the concentrations of Th1, Th17, and Treg cytokines in LPL from the large intestine, were measured. RESULTS: Se significantly ameliorated the symptoms of colitis and histological injury (P < 0.05 each), increasing the proportions of neutrophils and CD4+ CD25+ T cells (P < 0.05 each) and decreasing the proportions of γδT cells, CD4+, CD4+CD44+, and CD4+ CD69+ T cells in LPL (P < 0.05 each). Moreover, Se reduced the expression of IL-6, IFN-γ, IL-17A, IL-21, T-bet, and RORγt (P < 0.05 each), but enhanced the expression of IL-10 and Foxp3 (P < 0.05 each). CONCLUSION: These results suggest that Se protects against DSS-induced chronic colitis perhaps by increasing the number of CD4(+)CD25(+) Tregs that suppress the secretion of proinflammatory cytokines and populations of Th1, Th17, and γδT cells.

Dendritic cell vaccine modified by Ag85A gene enhances anti-tumor immunity against bladder cancer.

The ability of dendritic cells to provide all the signals required for T-cell activation makes them an ideal cancer vaccine platform. With the use of established DC2.4 cell line, originated from C57BL/6 mice and developed by superinfecting GM-CSF transduced bone marrow cells with myc and raf oncogenes, we investigated whether the DC 2.4 cell line transfected with Ag85A gene could enhance immunity against bladder cancer. Both phenotypic and functional analyses of Ag85A-DCs were done with use of FCM and T cell proliferation test. The cytotoxicity of Ag85A-DCs loaded with tumor cell lysate was verified by LDH. Finally, the production of interferon gamma was assayed by both ELISA and FCM. The immunotherapeutic effect of DC vaccine on murine bladder cancer was assessed pharmacologically and pathologically. Our results showed that Ag85A gene transfected DCs expressed high levels of key surface markers such as CD80, CD86 and MHC-II. The CTL primed with MB49 lysate-pulsed Ag85A-DCs elicits higher activity against MB49 tumor cells and upregulated level of IFN-γ production. Furthermore, the significant inhibitive effect on tumor growth in mice was found in the group of Ag85A-DC vaccine. The infiltration of CD4(+) or CD8(+) T cell within established tumor treated by Ag85A-DC vaccine significantly increased as compared with control groups. It is therefore concluded that DCs engineered by Ag85A gene exerts enhanced anti-tumor immunity against bladder cancer and this study might provide a meaningful mode of action with the use of Ag85A engineered DC vaccination in anti-cancer immunotherapy.

Opposite effects of Trichostatin A on activation of mast cells by different stimulants.

Mast cells (MCs) are activated upon stimulation via TLRs or FcepsilonRI, contributing to immune protection and/or leading to allergic diseases. In the present study, the effects of Trichostatin A (TSA) on the activation of MCs were analyzed with bone marrow-derived (BM) MCs. TSA increased the transcription and protein secretion of IL-6 in case of LPS-stimulation, in contrast to the suppressive effect on IgE-mediated activation of BMMCs. Chromatin immunoprecipitation assay showed IgE-mediated signaling-specific suppression of transcription factors recruitment to the IL-6 promoter. TSA-treatment inhibited nuclear translocation of NF-kappaB following IgE-mediated, but not LPS-induced activation in MCs.