Funded: February 2024
Funded by: The generosity of LJI Board Director Barbara Donnell, Bill Passey and Maria Silva, and various donors

Inflammation is a devastating force in autoimmune disease. Inflammation from wayward immune cells damages healthy cells and tissues. Normally, a protein called Foxp3 allows special regulatory T cells (Treg cells) to jump in and suppress this inflammation. When Treg cells lose Foxp3, they can transform into harmful ex-Treg cells. For my SPARK project, I am investigating the role of genetic material called transposable elements (TEs), once considered “junk” DNA, which are now recognized for their roles in inflammation and cancer. I hypothesize that Foxp3 represses TEs in Treg cells. When Foxp3 is lost, TEs increase, leading to inflammation.

I found that Treg cells without Foxp3 convert to ex-Treg cells, which secrete inflammatory substances and have higher levels of TEs. Foxp3 binds near TE sequences on DNA, regulating their expression. My work so far shows that reintroducing Foxp3 has a direct role in suppressing TEs. Targeting ex-Treg cells may prevent Tregs from becoming harmful, which could lead to new autoimmune disease treatments. Going forward, I will test drugs and gene editing to suppress TEs and reduce inflammation—aiming to develop innovative autoimmune disease therapies.