Decoding the CD4 T cell

In 2005, our lab reported a third lineage of effector CD4 T cells — Th17 cells — distinct from the Th1 and Th2 paradigms that had defined the field for two decades. That discovery reframed how immunologists think about inflammation and host defense.

Today we continue to dissect the transcriptional and metabolic circuitry that commits a naive T cell to the Th17 fate, the signals that keep that program stable or let it convert to other states, and how Th17 cells coordinate defense at barrier surfaces.

The intestine is the body's largest immune organ and a constant negotiation between tolerance and defense. We study how effector and effector-regulatory CD4 T cells develop in the gut, and how nuclear receptors and the microbiota shape their behavior.

Using reporter mice, fate-mapping, and single-cell approaches, we follow individual T cells through differentiation in their native tissue context — asking not just what a cell is, but how it got there and what it does next. An ongoing program asks how antigen presentation by the intestinal epithelium itself shapes these responses during infection, a question we are pursuing with single-cell atlases of the infected gut.

The same pathways that defend the gut can drive disease when dysregulated. Our work spans inflammatory bowel disease, the transition from chronic inflammation to colorectal cancer, and the mechanisms controlling late-onset sepsis in neonates.

By understanding how protective T-cell responses tip into pathology, we aim to identify points where they might be safely redirected — the foundation for more precise immunotherapies.