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Mouse study yields clue to why liver is less prone to rejection, say Pitt researchers

BOSTON, May 17 Researchers from the University of Pittsburgh's Thomas E. Starzl Transplantation Institute believe they have identified a mechanism that may help to explain why the liver enjoys privileged immunological status over other organs, making it the least vulnerable to rejection when transplanted.

Playing a central role in this mechanism is the dendritic cell, known for its ability to identify and present antigens, or foreign substances, to other immune system cells that are programmed to destroy the antigen. When mature, dendritic cells signal T cells, the soldiers of the immune system, to attack a transplanted organ, for example. But dendritic cells that reside in the liver are relatively docile in nature. Why this is, according to the Pitt study, may be due to the fact that they express lower amounts of a certain molecule that serves as a switch for the maturation process.

Reporting in a plenary session at the American Transplant Congress, the joint scientific meeting of the American Society of Transplant Surgeons and the American Society of Transplantation, An de Creus, Ph.D., identified the key molecule as a Toll-like receptor known as TLR-4. Toll-like receptors are like night watchmen that look for suspicious activity characterized by unusual patterns of other molecules. TLR-4 is known to react to lipopolysaccharide (LPS), a component found in the cell wall of bacteria. Reacting to LPS sets in motion a cascade of immune events that begins with the rapid maturation of dendritic cells.

Because of the liver's position downstream from the intestines, dendritic cells there encounter large amounts of LPS as remnants of bacteria from the gut are carried by blood flowing through the liver's portal vein. But unlike dendritic cells found elsewhere, such as in the spleen, dendritic cells that reside in the liver express less TLR-4, making them more apathetic toward LPS, the researchers found in their studies of mice.

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