""""""""The development of TID relies on interrelationships between cells of the immune system (e.g., DC, Teff, Treg), genes imparting susceptibility or resistance to the disease, and certain cytokines that appear key to the process underlying the autoimmune destruction of insulin producing pancreatic p cells."""""""" Variations on such a statement are common to most descriptions of TID to the point of serving as a central dogma for the pathogenesis of this disorder. While a broad body of evidence certainly exists to support this notion (and we ourselves believe it true), the exact mechanisms by which autoimmune (3 cell destruction is facilitated remain unclear. In addition, the relative contributions of each facet (i.e., cells, genes, cytokines) to the process remain, to a large extent, unknown. This forms a major void for attempts seeking to prevent and/or reverse the disease, as well as to identify improved biomarkers of disease progression &therapeutic efficacy. For these reasons, we deem it essential to perform the proposed research . Within this Specific Aims section of the POI overview, we identify our overall goals as well as the expected mechanistic / experimental outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI042288-15A1
Application #
8566443
Study Section
Special Emphasis Panel (ZAI1-PA-I (M1))
Project Start
Project End
Budget Start
2013-05-10
Budget End
2014-04-30
Support Year
15
Fiscal Year
2013
Total Cost
$404,897
Indirect Cost
$133,154
Name
University of Florida
Department
Type
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Perry, Daniel J; Wasserfall, Clive H; Oram, Richard A et al. (2018) Application of a Genetic Risk Score to Racially Diverse Type 1 Diabetes Populations Demonstrates the Need for Diversity in Risk-Modeling. Sci Rep 8:4529
Chen, Yi-Guang; Mathews, Clayton E; Driver, John P (2018) The Role of NOD Mice in Type 1 Diabetes Research: Lessons from the Past and Recommendations for the Future. Front Endocrinol (Lausanne) 9:51
Kusmartseva, Irina; Beery, Maria; Philips, Tiffany et al. (2018) Hospital time prior to death and pancreas histopathology: implications for future studies. Diabetologia 61:954-958
Hu, Ronghua; Xia, Chang-Qing; Butfiloski, Edward et al. (2018) Effect of high glucose on cytokine production by human peripheral blood immune cells and type I interferon signaling in monocytes: Implications for the role of hyperglycemia in the diabetes inflammatory process and host defense against infection. Clin Immunol 195:139-148
Smith, Mia J; Rihanek, Marynette; Wasserfall, Clive et al. (2018) Loss of B-Cell Anergy in Type 1 Diabetes Is Associated With High-Risk HLA and Non-HLA Disease Susceptibility Alleles. Diabetes 67:697-703
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Delitto, Daniel; Delitto, Andrea E; DiVita, Bayli B et al. (2017) Human Pancreatic Cancer Cells Induce a MyD88-Dependent Stromal Response to Promote a Tumor-Tolerant Immune Microenvironment. Cancer Res 77:672-683
Posgai, Amanda L; Wasserfall, Clive H; Kwon, Kwang-Chul et al. (2017) Plant-based vaccines for oral delivery of type 1 diabetes-related autoantigens: Evaluating oral tolerance mechanisms and disease prevention in NOD mice. Sci Rep 7:42372
Sebastiani, Guido; Ventriglia, Giuliana; Stabilini, Angela et al. (2017) Regulatory T-cells from pancreatic lymphnodes of patients with type-1 diabetes express increased levels of microRNA miR-125a-5p that limits CCR2 expression. Sci Rep 7:6897
O'Kell, Allison L; Wasserfall, Clive; Catchpole, Brian et al. (2017) Comparative Pathogenesis of Autoimmune Diabetes in Humans, NOD Mice, and Canines: Has a Valuable Animal Model of Type 1 Diabetes Been Overlooked? Diabetes 66:1443-1452

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