Summary
This project investigates how alterations in leukocyte integrin signaling, specifically a gain-of-function mutation in the SKAP2 gene, contribute to the development of type 1 diabetes (T1D) and associated autoimmunity.
Alterations of leukocyte integrin signaling leading to diabetes and autoimmunity
US · IL
NIH
grant
open
#nih-5R01AI170841-04
What they want
The project proposes to complete the analysis of NOD.SKAP2 KI mice, which model autoimmune T1D, under the hypothesis that increased cell adhesion in dendritic cells leads to prolonged DC-T cell interactions, driving selection of auto-reactive T-cell clones and T1D. This will involve adoptive cell transfer experiments, generation of conditional knock-in mice, and imaging of DC-T cell interactions in inflamed islets. Similar studies will be performed for other candidate leukocyte integrin signaling mutations identified in a monogenic T1D registry.
