Exploring the Interplay between Fatty Acids, Inflammation, and Type 2 Diabetes.

Around 285 million people worldwide currently have type 2 diabetes and it is projected that this number will be surpassed by 2030. Therefore, it is of the utmost importance to enhance our comprehension of the disease's development. The regulation of diet, obesity, and inflammation in type 2 diabetes is believed to play a crucial role in enhancing insulin sensitivity and reducing the risk of onset diabetes.

Tracking of an Oral -Based Vaccine for Type 1 Diabetes in Non-obese Diabetic Mice.

Type 1 diabetes (T1D) arises secondary to immune-driven destruction of pancreatic β-cells and manifests as insulin-deficient hyperglycemia. We showed that oral vaccination with live attenuated , which simultaneously delivers autoantigens and a TGFβ expression vector to immune cells in the gut mucosa, provides protection against the progression of T1D in non-obese diabetic (NOD) mice. In this study we employed the Sleeping Beauty (SB) transposon system that is composed of a transposase and transposon encoding the td-Tomato to express red fluorescent protein (RFP) to permanently mark the cells that take up the vaccine.

Reversal of New Onset Type 1 Diabetes by Oral -Based Combination Therapy and Mediated by Regulatory T-Cells in NOD Mice.

Autoimmune diseases such as type 1 diabetes (T1D) involve the loss of regulatory mechanisms resulting in increased tissue-specific cytotoxicity. The result is destruction of pancreatic insulin-producing β-cells and loss of glucose homeostasis. We are developing a novel oral vaccine using live attenuated to deliver TGFβ, IL10, and the diabetic autoantigen preproinsulin combined with low-doses of anti-CD3 mAb.

The Role of Dendritic Cell Maturation in the Induction of Insulin-Dependent Diabetes Mellitus.

Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans and are largely responsible for the initiation and guidance of innate and adaptive immune responses involved in maintenance of immunological homeostasis. Immature dendritic cells (iDCs) phagocytize pathogens and toxic proteins and in endosomal vesicles degrade them into small fragments for presentation on major histocompatibility complex (MHC) II receptor molecules to naïve cognate T cells (Th0). In addition to their role in stimulation of immunity, DCs are involved in the induction and maintenance of immune tolerance toward self-antigens.

Chimeric Vaccine Stimulation of Human Dendritic Cell Indoleamine 2, 3-Dioxygenase Occurs via the Non-Canonical NF-κB Pathway.

A chimeric protein vaccine composed of the cholera toxin B subunit fused to proinsulin (CTB-INS) was shown to suppress type 1 diabetes onset in NOD mice and upregulate biosynthesis of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1) in human dendritic cells (DCs). Here we demonstrate siRNA inhibition of the NF-κB-inducing kinase (NIK) suppresses vaccine-induced IDO1 biosynthesis as well as IKKα phosphorylation. Chromatin immunoprecipitation (ChIP) analysis of CTB-INS inoculated DCs showed that RelB bound to NF-κB consensus sequences in the IDO1 promoter, suggesting vaccine stimulation of the non-canonical NF-κB pathway activates IDO1 expression in vivo.

Induction of indoleamine 2, 3-dioxygenase in human dendritic cells by a cholera toxin B subunit-proinsulin vaccine.

Dendritic cells (DC) interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1).