Project Description

Many genetic mutations are linked to the risk for developing type 1 diabetes (T1D). One such mutation is found in the CD226 gene, which encodes a receptor that increases the activation of T cells – the primary immune cells responsible for destroying insulin-producing pancreatic beta-cells. 

Our group has shown that CD226 can impair the function of human regulatory T cells (Treg), a subset of immune cells critical for maintaining self-tolerance, a term that refers to the immune system’s ability to determine which antigens to attack and which ones to leave alone. 

We hypothesize that CD226 may contribute to T1D by supporting the development of rogue immune cells known as exTregs. Furthermore, we propose that therapeutics inhibiting the CD226 pathway may prevent T1D due to improved Treg function.

Our previous work showed that interruption of the CD226 gene inhibits T1D development in the non-obese diabetic (NOD) mouse model. This finding supports a need for research that explore how CD226 contributes to T1D onset and a need for therapies that prevent TID by targeting this gene. 

In our investigation, we will study the ways that CD226 impairs Treg function by comparing immune cells in tissues from mice with the cD226 gene deleted to cells from mice with the gene intact. We will also compare mice with the CD226 deletion to fluorescent reporter mice with exTreg cells intact. Further studies will assess whether the loss of CD226 affects Treg generation in ways beyond their suppressive function.

We will also assess two strategies for CD226 inhibition in the NOD mouse model. First, we will test how effectively a CD226 blocking antibody at inhibits T1D development. Second, we will measure how well depleting CD226-expressing Tregs improves Treg isolation, expansion, and re-infusion therapy for the prevention of T1D. These studies will improve our knowledge of the role CD226 plays in T1D development. And we expect the preclinical data we generate will support the initiation of clinical studies of CD226-targeting therapeutics designed to prevent T1D. 

Click HERE to view Dr. Shapiro’s video.