White blood cells play an important role in the immune response. They are often perceived as brave soldiers, ready to attack invaders hoping to take over the body. Yet they sometimes turn on the body instead.
André Veillette and Dominique Davidson of the Institut de recherches cliniques de Montréal (IRCM) / Montreal Clinical Research Institute recently shed light on one of the mechanisms that controls a type of white cell called T cells, or T lymphocytes. Their discovery was recently published in Cell Reports.
A tough puzzle
“Some people’s T cells overreact, causing autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, lupus and graft versus host reactions,” explains André Veillette, Director of the IRCM Molecular Oncology research unit and professor at Université de Montréal and McGill University. “That’s why we want to understand the mechanisms that, under normal circumstances, control T cell function.”
It was already known that an enzyme called Csk could bind to T cell membranes and therefore control T cells, preventing them from overreacting. But the scientific community was unable to demonstrate what made Csk bind to T cell membranes, thus enabling it to function. After many years of perseverance, Dominique Davidson, Senior Research Associate in Dr. Veillette’s group, has found the key to the mystery.
“A third molecule—PAG—is involved,” explains Dr. Davidson. “It is embedded in T cell membranes, and attracts Csk like a magnet. In short, PAG is essential in recruiting Csk to T cell membranes and controlling T cell activity, making sure T cells do not become hyperactive.”
The mechanism has long been examined in the research community, but until now no one had clearly demonstrated how it works.
“The key to the mystery lay in pre-stimulating the immune system of our PAG deficient mice,” explains Dr. Veillette. “Prior to the first stimulation, the PAG deficient T cells are no different. But during subsequent stimulations, T cell response increases.”
About the study
The research project was conducted at the IRCM Molecular Oncology research unit by Dominique Davidson, Ming-Chao Zhong and André Veillette. Pier Paolo Pandolfi of the Beth Israel Deaconess Cancer Center, Silvia Bolland of the National Institute of Allergy and Infectious Diseases, Ramnik J. Xavier of the Broad Institute of MIT and Harvard, Brian Seed of Massachusetts General Hospital, as well as Xin Li and Hua Gu of the IRCM Molecular Immunology research unit, were also involved in the study. The research was funded by the Canadian Institutes of Health Research and Canada Research Chairs Program.
About the IRCM
Founded in 1967, the Institut de recherches cliniques de Montréal (IRCM) / Montreal Clinical Research Institute is a non-profit organization that conducts fundamental and clinical biomedical research in addition to training high-level young scientists. With its cutting-edge technology facilities, the institute brings together 33 research teams, which work in cancer, immunology, neuroscience, cardiovascular and metabolic diseases, systems biology and medicinal chemistry. The IRCM also operates a research clinic specialized in hypertension, cholesterol, diabetes and cystic fibrosis, as well as a research centre on rare and genetic diseases in adults. The IRCM is affiliated with the Université de Montréal and associated with McGill University. Its clinic is affiliated with the Centre hospitalier de l’Université de Montréal (CHUM). The IRCM is supported by the Ministère de l’Économie, de la Science et de l’Innovation (Quebec ministry of Economy, Science and Innovation).
Source:
Anne-Marie Beauregard, Communication Advisor
Institut de recherches cliniques de Montréal (IRCM) / Montreal Clinical Research Institute
514 987-5555 | anne-marie.beauregard@ircm.qc.ca
