Hamster IL-17 (Interleukin 17) ELISA Kit

Objective: The pathogenesis and mechanism of colitis may be related to intestinal flora, genetic susceptibility, environmental and immune factors. Among these various factors, the importance of environmental factors in the pathogenesis of colitis has been increasingly recognized. The purpose of this study was to investigate the effects of hypoxia on intestinal mucosal immunity. Methods: Experimental colitis was induced by oral gavage of Citrobacter rodentium (C. rodentium) in mice, then divided into normoxia group and hypoxia group. Mice were sacrificed after 2 weeks. Physiological and blood biochemical indicators were monitored to verify the hypoxia model. The body weight, fecal bacterial output, colon length and colon histopathology were observed to evaluate severity of colitis. The concentration of cytokines in colonic tissues were detected by ELISA. The percentage of CD4(+) IFN-gamma(+) (Th1) and CD4(+) IL-17(+) (Th17) cells in mesenteric lymph nodes (MLN) were detected by flow cytometry. The levels of mucosal antimicrobial peptides (AMPs), related inflammatory factors and transcription factors in colon tissues were detected by qRT-PCR. Results: Mice in hypoxic C. rodentium infection (Hypoxia + C.r.) group exhibited significant decrease in body weight, increase in fecal bacterial pathogen output, and more severe histopathological damage in the colon compared with the C. rodentium infection (Nomoxia + C.r.) group. Meanwhile, the level of NF-kappa B, TLR4, COX-2, IL-6 and TNF-alpha of colonic tissue were increased, while IL17, IL-22, and Reg3 gamma were decreased. The percentage of CD4(+) IFN-gamma(+) (Th1) and CD4(+) IL-17(+) (Th17) cells in MLN were significantly decreased in mice of Hypoxia + C.r. group, accompanied by the decreased of IFN-gamma and IL-17. In addition, the level of the T-bet ROR gamma t, IL-12 and IL-23 were decreased in mice of Hypoxia + C.r. group. Conclusions: Hypoxic exposure significantly exacerbates the symptoms and the pathological damage of mice with colitis and influences the immune function by down-regulating Th1 and Th17 responses in C. rodentiuminduced colitis in mice.

Purpose: Innate immunity is an indispensable arm of tumor immune surveillance, and the liver is an organ with a predominance of innate immunity, where mucosal-associated invariant T (MAIT) cells are enriched. However, little is known about the phenotype, functions, and immunomodulatory role of MAIT cells in hepatocellular carcinoma (HCC). Experimental Design: The distribution, phenotype, and function of MAIT cells in patients with HCC were evaluated by both flow cytometry (FCM) and in vitro bioassays. Transcriptomic analysis of MAIT cells was also performed. Prognostic significance of tumor-infiltrating MAIT cells was validated in four independent cohorts of patients with HCC. Results: Despite their fewer densities in HCC tumor than normal liver, MAIT cells were significantly enriched in the HCC microenvironment compared with other mucosaassociated organs. Tumor-derived MAIT cells displayed a typical CCR7(+) CD45RA(+) CD45RO(+) CD95(+) effector memory phenotype with lower costimulatory and effector capabilities. Tumor-educatedMAIT cells significantly upregulated inhibitory molecules like PD-1, CTLA-4, TIM-3, secreted significantly less IFNg and IL17, andproducedminimal granzyme B and perforin while shifting to produce tumor-promoting cytokines like IL8. Transcriptome sequencing confirmed that tumor-derived MAIT cells were reprogrammed toward a tumor-promoting direction by downregulating genes enriched in pathways of cytokine secretionand cytolysis effector function likeNFKB1 and STAT5B and by upregulating genes like IL8, CXCL12, and HAVCR2 (TIM-3). High infiltration of MAIT cells in HCC significantly correlated with an unfavorable clinical outcome, revealed by FCM, qRT-PCR, and multiplex IHC analyses, respectively. Conclusions: HCC-infiltrating MAIT cells were functionally impaired and even reprogrammed to shift away from antitumor immunity and toward a tumor-promoting direction.