Thesis Cytokine Cd4

Collectively, this study suggests that subchronic, low-dose cadmium exposure impacts both immune cell function and cellularity, and may enhance inflammatory responses. Wiley Online Library requires cookies for authentication and use of other site features; therefore, cookies must be enabled to browse the site.To discover other potentially important cytokine networks, I developed a novel analysis pipeline to reconstruct and compare cytokine networks from whole tumor gene expression data.

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Cadmium is a toxic metal and common environmental contaminant.

Chronic cadmium exposure results in kidney, bone, reproductive, and immune toxicity as well as cancer.

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IL-6 is an inflammatory cytokine that contributes to the pathogenesis of many immunological diseases including rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, allergic asthma, as well as the protection against infections caused by various pathogens.

The cytokine milieu in the tumor microenvironment plays a key role in modulating the immune response either in favor of or against tumorigenesis.

For many tumors, this complex network of cytokine and immune interactions represent a formidable means of escape from immune surveillance.In recent years, Th17 cells have emerged as a key player in host defense against both extracellular pathogens and fungal infections.Th17 cells have also been implicated as one of the main drivers in the pathogenesis of autoimmune diseases such as multiple sclerosis, which are likely mediated in part by the cytokines that Th17 cells produce.Cadmium induces splenomegaly and affects the adaptive immune system, but specific effects vary depending on the dose, model, and endpoint.This study investigates the effects of subchronic, oral, and low-dose cadmium exposure (32 ppm cadmium chloride in drinking water for 10 weeks) on the rat immune system, focusing on T cell function.Cadmium-exposed animals demonstrated slight increases in the spleen-to-body weight ratios, and decreases in overall splenic cell numbers and markers of oxidative stress.The relative ratios of splenic cell populations remained similar, except for modest increases in regulatory T cells in the cadmium-exposed animals.In this thesis, we identify a novel molecular mechanism by which IL-6 regulates CD4 T cell effector function.We show that IL-6-dependent signal raises the levels of mitochondrial Ca2 late during activation of CD4 T cells.These cytokine networks are particularly important in pancreatic ductal adenocarcinoma (PDA), where a prominent infiltration of immunosuppressive immune populations could be found.Myeloid-derived suppressor cells (MDSCs) have previously been shown to be potent suppressors of anti-tumor immunity in PDA, but the cytokine networks regulating their recruitment to the tumor microenvironment remain incompletely understood.


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