A research team led by Xian Chang Li, MD, PhD, Brigham and Women's Hospital (BWH) Transplantation Research Center, has shed light on how a population of lymphocytes, called CD4+ T cells, mature into various subsets of adult T helper cells.
In particular, the team uncovered that a particular cell surface molecule, known as OX40, is a powerful inducer of new T helper cells that make copious amounts of interleukin-9 (IL-9) (and therefore called TH9 cells) in vitro; such TH9 cells are responsible for ongoing inflammation in the airways in the lungs in vivo.
The study will be published online in Nature Immunology on July 29, 2012.
In their studies, the researchers found that mice with hyper-active OX40 activities had signs of tissue inflammation, particularly in tissues lining the airway. A high amount of cells—as much as 30 percent—in these tissues were mucin-producing cells. Mucin-producing cells produce gel-like secretions that, when combined with other secretions, can form mucus or saliva.
The results mirrored previous studies of mice who over expressed IL-9 in the lung airways. Results from additional experiments confirmed that OX40 triggers both TH9 cell and IL-9 production, thereby leading to airway inflammation.
"These findings may have broad impact on how to treat chronic inflammation, such as allergic inflammation and chronic allograft rejection after transplantation, since the inflammatory texture organized by TH9 cells tends to be different and ongoing." said Li.
In addition to this translational finding, Li and his team made strides in better understanding OX40's role in the molecular mechanisms of the pathway responsible for TH9 cell induction.
According to Li, the revelation that OX40 promotes TH9 cells through TRAF6 (a protein that mediates cell signaling) and the activation of a non-canonical NF-kB pathway will point to new opportunities in drug discovery and development in treatment of TH9-related diseases.
This research was supported by the United States National Institutes of Health and the Juvenile Diabetes Research Foundation International.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs nearly 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $625 million in funding.
BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies, OurGenes and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.
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