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Genetic evidence points to potential therapeutic bypass for autoimmune process
Date:3/2/2009

CINCINNATI Bypassing a molecular breakdown that helps trigger autoimmunity could lead to new treatments for autoimmune disorders and chronic infections that sicken or kill thousands of children annually, according to researchers.

A study in the March 2 PLoS Biology has discovered genetic evidence that two distinct molecular pathways control the formation of regulatory T cells (Treg), a vitally important cell type in limiting undesirable immune responses. Autoimmunity is where the immune system mounts a self attack on the body, destroying vital tissues and organs.

Treg cells control the vigor of T cell responses. If the body lacks sufficient numbers of Treg cells, it loses the ability to tone down immune responses once invading pathogens are cleared. In addition, the body is unable to suppress T cell responses that recognize and target "self" antigens in the body. The latter can lead to autoimmunity.

Under normal healthy conditions, the majority of Treg cells are derived from an organ called the thymus. However, the study shows that in the functional absence of a gene called Carma1, Treg development is impaired in the thymus. Mutations in Carma1 can result in a failure of the thymus to produce Treg cells, said senior investigator Kasper Hoebe, Ph.D., a researcher in the Division of Molecular Immunology at Cincinnati Children's Hospital Medical Center.

But the study also points to a second molecular pathway occurring in the peripheral lymphoid system that can result in development of Treg cells. This means if the process in the thymus breaks down, as in the case with Carma1 mutations, inducing Treg cells through the peripheral lymphoid system may fill the void, according to the investigators.

"We show there are essentially two independent pathways for Treg development, and that it can occur quite well in the peripheral lymphoid system, independent of the thymic process," Dr. Hoebe said. "This is important be
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Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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