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Discovery of T-cell 'traffic control' boosts new drug promise

Scientists have begun to clarify how one of the body's molecules controls the trafficking of T cells through the blood, lymph nodes and on to tissues to fight infection -- a crucial response that sometimes goes awry, attacking the body's own tissues and causing autoimmune diseases.

The traffic control system -- composed of a fat-like compound called S1P and its receptor on T cells -- usually prevents T cells from launching harmful reactions. But when the S1P traffic cop reacts incorrectly, T cells can swamp healthy tissue. The new research explains how a promising experimental drug treats the autoimmune disease multiple sclerosis by blocking excess S1P action. The research also shows the promise of similar strategies to prevent rejection of transplanted organs and tissues without compromising essential immune defenses.

The emerging view brings together research findings on S1P's effect on both the immune system and the blood-circulating vascular system, showing how the two systems interact to regulate T cell circulation and prevent a constant and potentially dangerous release of T cells, or lymphocytes.

The research is presented this month in a special issue of Nature Reviews Immunology. Authors are Edward Goetzl, MD, at UCSF and Hugh Rosen, MD, PhD, at the Scripps Research Institute, scientists who have pioneered the new understanding. Goetzl is the Robert L. Kroc Professor of Medicine and Immunology at UCSF. Rosen is a professor of immunology at Scripps.

Goetzl and Rosen participated in the discovery of S1P's role in T cell trafficking. Goetzl has also shown that S1P regulates T cell trafficking by occupying a receptor on the T cell surface that suppresses the cells' normal response to a "forward march" signal.

T cells respond by chemotaxis -- moving from areas of lower to higher concentration of a signaling molecule known as a chemokine. Studies by the two scientists have shown that S1P and its T cell receptors block this si
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Source:University of California - San Francisco


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