Luc Teyton, professor in the Department of Immunology and Microbiology at Scripps Research, has secured a five-year, $3.2 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This funding aims to unravel the mechanisms of type 1 diabetes and develop potential therapeutics to prevent or reverse the disease.
Type 1 diabetes is an autoimmune disorder where the immune system erroneously attacks insulin-producing cells. Approximately 1.6 million Americans are affected, yet the precise triggers remain elusive. Teyton, alongside Assistant Professor Joseph Jardine, will investigate vascular-associated fibroblastic cells (VAFs) in this context. VAFs, though rare, are crucial for safeguarding insulin-producing cells in the pancreas. Initial findings suggest that type 1 diabetes may arise when VAFs are overwhelmed, leading to immune-mediated destruction of insulin-producing cells.
Teyton’s recent study, published in Cell Reports, identified VAFs presenting pancreatic antigens to the immune system — a role usually reserved for specialized immune cells. VAFs also emit inhibitory signals, maintaining a protective environment. However, persistent inflammation heightens antigen presentation without increasing inhibitory signals, potentially triggering an immune response against insulin-producing cells.
This discovery challenges the longstanding view that type 1 diabetes originates within pancreatic islets. Instead, Teyton’s research shows immune cells congregating outside the islets, with VAFs acting as intermediaries. “We’ve been looking in the wrong place,” Teyton notes, highlighting the significance of these boundary cells in disease onset.
The NIDDK grant will facilitate a comprehensive analysis of antigen-presenting cells in pancreatic islets, focusing on changes as the disease progresses. Teyton’s team will also explore why VAFs present peptide fragments rather than whole proteins and how inflammation disrupts pancreatic function. Recent evidence suggests that diet and gut-derived factors could play a role, prompting further investigation into these pathways.
The research, supported by NIDDK grant #1UG3DK142188-01, will employ models to study type 1 diabetes initiation and progression. Understanding the triggers of VAF transformation could reveal novel intervention points, potentially paving the way for new therapeutic approaches.
