Pathogenesis to Targeted Treatment for a T1D Risk Locus

The costimulatory molecule CD226 is highly expressed on effector/memory CD8+ T cells and genetic polymorphisms in CD226 have been associated with T1D susceptibility. We identified the role of CD226 in human and murine CD8+ T cell activation and regulatory T cell (Treg) instability and found that in vivo treatment with a CD226 blocking antibody inhibited T1D progression in the non-obese diabetic (NOD) mouse model.

Publications

Inhibition of CD226 co-stimulation suppresses diabetes development in the NOD mouse by augmenting regulatory T cells and diminishing effector T cell function

Matthew E Brown, P. Thirawatananond, Leeana D. Peters, Elizabeth J Kern, Sonali Vijay, Lindsey K. Sachs, A. Posgai, Maigan A. Brusko, Melanie R. Shapiro, Clayton E. Mathews, Rhonda L. Bacher, Todd M. Brusko

Diabetologia, 2024

Treg-Specific CD226 Deletion Reduces Diabetes Incidence in NOD Mice by Improving Regulatory T-Cell Stability

P. Thirawatananond, Matthew E Brown, Lindsey K. Sachs, Juan M. Arnoletti, Wen-I Yeh, A. Posgai, Melanie R. Shapiro, Yi-Guang Chen, T. Brusko

Diabetes, 2023

Human CD4+CD25+CD226- Tregs Demonstrate Increased Purity, Lineage Stability, and Suppressive Capacity Versus CD4+CD25+CD127lo/- Tregs for Adoptive Cell Therapy

Matthew E Brown, Leeana D. Peters, Seif R. Hanbali, Juan M. Arnoletti, Lindsey K. Sachs, Kayla Q. Nguyen, Emma B. Carpenter, Howard R. Seay, C. Fuhrman, A. Posgai, Melanie R. Shapiro, T. Brusko

Frontiers in Immunology, 2022

CD226 Deletion Reduces Type 1 Diabetes in the NOD Mouse by Impairing Thymocyte Development and Peripheral T Cell Activation

Melanie R. Shapiro, Wen-I Yeh, Joshua R. Longfield, J. Gallagher, Caridad M. Infante, Sarah Wellford, A. Posgai, M. Atkinson, M. Campbell-Thompson, S. Lieberman, D. Serreze, A. Geurts, Yi-Guang Chen, T. Brusko

Frontiers in Immunology, 2020