Ivy Debreceni

Pathogenic role of CD226 in lacrimal gland autoimmunity in the non-obese diabetic mouse model of Sjögren Syndrome

Sjögren syndrome is an autoimmune disease that targets lacrimal and salivary glands through immunopathogenic mechanisms that leads to debilitating poor oral and ocular health. Though it is estimated to affect 4 million people in the US alone, this number is potentially underrepresented due to limited ability to detect early stages of disease. The absence of adequate early diagnostics contributes to the lack of effective therapies to halt the autoimmune process. Non-obese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity with features similar to human disease such as: focal inflammation of the glands, autoantibody formation, and gland dysfunction. The NOD mouse model is a fundamental tool to study the development of Sjögren syndrome-like autoimmunity.

CD226 is a cell surface glycoprotein that is a member of the immunoglobulin super family and expressed on hematopoietic cells. Crosslinking CD226 on T cells causes activation and differentiation towards proinflammatory phenotypes. A polymorphism of CD226 has been linked to several autoimmune diseases but CD226 has not been implicated to play a role in Sjögren Syndrome. However, Cd226 is required for lacrimal gland autoimmunity in our model. Additionally, another receptor on T cells, T Cell immunoreceptor with IG and ITIM domains (TIGIT) binds the same ligands as CD226, but with a higher affinity. TIGIT expression has a positive correlation with FoxP3 expression on CD4+ Tregs and TIGIT signaling leads to immunoregulatory effects. The CD226/TIGIT axis has been shown to play a role in other autoimmune diseases, cancer, and graft rejection. The long-term goal of my research is to elucidate the early mechanisms of lacrimal and salivary gland autoimmunity and to understand the effector/regulatory balance that the CD226/TIGIT axis plays in Sjögren syndrome like autoimmunity.

Honors and Awards

  • AAI Young Investigator award, 2019
  • 3-Minute Thesis Finalist 2020
Ivy Debreceni
Elmer, NJ
BS, Biological Sciences, Drexel University

2191 ML
United States

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