Whether it's Multiple Sclerosis, Type 1 Diabetes, Lupus, or Crohn's Disease, autoimmunity is a rapidly growing problem that traditional pharmaceuticals have failed to completely cure. While these diseases have very different symptoms, they all have the same root cause -- the body’s immune system is attacking its own healthy organs. Lurking within ourselves are a group of T cells called regulatory T cells that have the power to suppress immune function. These cells have huge potential to be engineered and utilized as a platform to cure any autoimmune disease. Unfortunately, they easily lose their suppressive abilities and can even exacerbate autoimmunity if handled incorrectly. Looking to stabilize regulatory T cells, Jessica and her colleagues perform a CRISPR screen to map which genes are responsible for maintaining their suppressive function. Using this data, Jessica takes the first step to bring this incredibly powerful cell type to the clinic to help millions of patients suffering from a myriad of diseases.

About the Author

• Jessica performed this work in the lab of Professor Alex Marson at the University of California, San Francisco. The Marson lab is renowned for their work in building and applying synthetic biology tools to understand and improve the therapeutic value of immune cells.
• Jessica is driven to understand and cure autoimmune diseases because her mother, her sister, and her have all been diagnosed with autoimmune diseases.

Key Takeaways

• Regulatory T cells can suppress immune reactions, making them an attractive therapeutic to be used to cure any autoimmune disease.
• These regulatory T cells do not easily maintain their suppressive function, necessitating some engineering to make sure they maintain their therapeutic value.
• With CRISPR, Jessica turned every gene off one-by-one in regulatory T cells to find which genes were involved in maintaining its suppressive function.
• Jessica found a gene, USP22, that when expressed, inhibited regulatory T cell function making it a useful target for both autoimmunity and cancer.

Translation

• While Jessica focused on one of the hits from the screen, there were many more that have massive potential as drug targets or as engineering steps for T cell therapies against autoimmunity.
• Maintaining a stable regulatory T cell is the vital first step to creating a world where all autoimmune diseases are cured using cells.

First Author: Jessica Cortez

Paper: 

CRISPR screen in regulatory T cells reveals modulators of Foxp3