Overactive STAT3 weakens CD8 T cells by raising CD39 levels
Chronic STAT3 signaling in STAT3 GOF causes CD8 T cell dysfunction via CD39 upregulation
This project examines whether people with STAT3 gain‑of‑function mutations have more CD39 on CD8 T cells, making those cells less able to fight viruses and more likely to contribute to autoimmune problems.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Children's Hosp of Philadelphia NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11250043 on NIH RePORTER |
What this research studies
Researchers will study blood and immune cells from patients with STAT3 gain‑of‑function (GOF) to measure CD39 levels and CD8 T cell function. They will use mouse models that mimic STAT3 GOF to track how increased CD39 drives ATP breakdown to adenosine and how that signal dampens CD8 responses. The team will measure ATP hydrolysis, adenosine signaling through the A2A receptor, and CD8 cytokine production and proliferation. They will test whether blocking CD39 or A2A signaling can restore CD8 function in model systems with the goal of informing future patient therapies.
Who could benefit from this research
Good fit: People diagnosed with STAT3 gain‑of‑function mutations, especially children with recurrent viral infections and autoimmune symptoms, are the ideal candidates.
Not a fit: People without STAT3 GOF mutations or whose immune problems are caused by unrelated conditions are unlikely to gain direct benefit from this project.
Why it matters
Potential benefit: If successful, this work could point to CD39 or A2A receptor blockade as strategies to improve antiviral immunity and reduce harmful autoimmunity in people with STAT3 GOF.
How similar studies have performed: Targeting the CD39/adenosine pathway has shown promise in preclinical work and in some cancer immunotherapy trials, but applying these approaches specifically to STAT3 GOF is a new translational step.
Where this research is happening
Philadelphia, United States
- Children's Hosp of Philadelphia — Philadelphia, United States (Active)
Researchers
- Principal investigator: Henrickson, Sarah E — Children's Hosp of Philadelphia
- Study coordinator: Henrickson, Sarah E
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.