Penn Researchers Describe Key Molecule That Keeps Immune Cell Development on Track

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Media Contact:Karen Kreeger | Karen.kreeger@uphs.upenn.edu | 215-349-5658August 8, 2011

Philadelphia ‚ÄĒ In the latest issue of Nature, researchers at the Perelman School of Medicine at the University of Pennsylvania clarify the role of two proteins key to T-cell development. They found that one well-known protein called Notch passes off much of its role during T-cell maturation to another protein called TCF-1. T cells are required for many aspects of immunity, and understanding how these proteins influence the production of infection-fighting cells could improve treatments for immune-suppressed patients.

The research group, led by senior author Avinash Bhandoola, MBBS, PhD, associate professor of Pathology and Laboratory Medicine, found an important role in early T-cell development for T-cell factor 1 (TCF-1), which is turned on by Notch signals.

"Notch triggers the process of T-cell development, and turns on expression of TCF-1, but Notch itself doesn't stick around; it's more of a kiss-and-run molecule," says Bhandoola. In contrast, once induced by Notch, TCF-1 is faithfully expressed throughout T-cell maturation.

T cells are made in the thymus, a small organ situated under the breastbone near the heart. However, T cells, like all blood-cell types, originate from blood-producing stem cells in the bone marrow. Immature T-cell progenitors leave the bone marrow, settle within the thymus, and eventually give rise to T cells.

Notch regulates cell-fate decisions in many cell types in addition to immune cells. Past work at Penn helped demonstrate that Notch is active in early T-cell progenitors in the thymus of mice, and drives the differentiation of these progenitors down the T cell pathway.

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