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A protein found in the nucleus of blood-derived cells plays a key role in the regulation of the immune system and could provide a target for the development of new treatments for a number of conditions and diseases ranging from asthma to cancer, according to researchers at Children’s Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine. The findings are available online today in the journal Science Translational Medicine.
Researchers led by Yatin Vyas, M.D., discovered that Wiskott-Aldrich syndrome protein (WASp), which was known to be present in the cell cytoplasm, also is present in the nucleus of cells. The team’s most significant finding is that this nuclear WASp regulates the activation of a set of genes that control development of T-helper type 1(Th1) cells, a subset of lymphocytes crucial to a healthy immune system.
“Without enough WASp present in the nucleus, Th1 immunity is impaired, and this type of immunity is required to combat most infections and many cancers,” said Dr. Vyas, a hematologist/oncologist at Children’s Hospital and an assistant professor of pediatrics at the University of Pittsburgh School of Medicine. “This finding significantly expands our understanding of the importance of WASp in the biology of the immune cell and its potential as a therapeutic target in certain immune disorders.”
According to Dr. Vyas, if Th1 immune cells are deficient, another group of immune cells known as T-helper type 2 (Th2) dominates the immune system. Overexpression of Th2 cells is known to lead to autoimmune conditions such as asthma and colitis.
Dr. Vyas’ discovery occurred while researching a condition known as Wiskott-Aldrich syndrome (WAS), a genetic disease that occurs in boys. Patients with WAS have a defective immune system resulting in severe, life-threatening infections. Many children with WAS develop conditions such as hemolytic anemia, low platelets, neutropenia, eczema, arthritis, vasculitis, inflammatory bowel disease and kidney disease. They also are prone to blood cancers such as leukemia and lymphoma. Previous research has shown that WAS patients experience a loss of function of the WAS protein, which is present in white blood cells and platelets.
“WASp appears to function as a nuclear protein that participates in the T cell’s gene activation program and plays an important role in the balance of the two arms of the immune responses, Th1 and Th2,” Dr. Vyas said. “Our discovery could have far-reaching implications to the development of diseases caused by the imbalance of Th1 and Th2 responses. Now that we have identified that WASp is present in the nucleus, we are interested in exploring the details of how this protein might function in gene activation and the overall integrity of chromosomes in the immune cells.”
The National Institutes of Health funded this study.
Renowned for its outstanding clinical services, research programs and medical education, Children’s Hospital of Pittsburgh of UPMC has helped establish the standards of excellence in pediatric care. From ambulatory care to transplantation and cardiac care, talented and committed pediatric experts care for infants, children and adolescents who make more than 1 million visits to Children’s, its many neighborhood locations and Children’s Community Pediatrics practices each year.
Children’s also has been named consistently to several elite lists of pediatric health care facilities, including ranking tenth in total dollars and seventh in number of awards (NIH FY 2008) in funding provided by the National Institutes of Health (NIH), and is named one of the top pediatric hospitals in the United States by U.S. News & World Report. For more information about Children’s Hospital, visit www.chp.edu.
As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see www.medschool.pitt.edu.
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