From the NOD Mouse to Patients: Type 1 Conventional Dendritic Cells as a Therapeutic Target in Type 1 Diabetes

Type 1 diabetes (T1D) is an autoimmune disease characterized by CD8⁺ T cell mediated destruction of pancreatic β cells, leading to insulin deficiency. The non-obese diabetic (NOD) mouse is widely used as an experimental model for T1D because it closely mirrors the genetic and immune characteristics of the human disease. One key similarity between human T1D and the NOD mouse model is the associated HLA/MHC class II variant that alters the repertoire of CD4⁺ T cells potentially leading to the initiation of disease. In addition, type 1 conventional dendritic cells (cDC1s) play an essential role in disease development through cross-presentation of β-cell antigens to CD8⁺ and CD4⁺ T cells. Notably, inhibiting this cross-presentation has been shown to prevent T1D in NOD mice. Therefore, as we strive to find strategies to inhibit T1D onset and progression, insights from NOD mice provide important guidance for understanding human T1D and for developing targeted immunotherapies.