Houston Methodist Hospital researchers have discovered a way to activate certain T-cells to potentially prevent autoimmune diseases and organ transplant rejection.
T-cells are a type of white blood cell that play a central role in protecting the body from infection and transplant rejection.
Wenhao Chen, M.D., Ph.D., a scientist in the Immunobiology and Transplant Science Center at the Houston Methodist Research Institute, has been investigating T-cell biology for the past 20 years.
Recently, he and colleagues from Houston Methodist and Union Hospital at Huazhong University of Science and Technology in China identified the molecules in T-cells that control function and found a way to target them to help treat infection and disease.
“T-cells are important, so if you know the basic biology—how they are activated and how they function in different models—you can begin to solve those issues,” Chen said.
All About T-cells
T-cells are different from other cells in that they want to protect the body, Chen explained. Because T-cells are antigen-specific, not all will respond to a particular toxic or foreign substance. Yet a very small number of T-cells will recognize a foreign substance, can be activated and expanded in just days to respond to it.
The T-cell receptor or TCR sends its activation signal to T-cells and induces the expression of hundreds of genes and molecules that allow T-cells to either attack transplants or fight infection. A positive result occurs when the T-cells get rid of infected cells; a negative result occurs when the T-cells reject transplanted tissues.
Chen and his team hypothesized that if they could identify the molecular targets in activated T-cells, they could inhibit the function of the activated T-cells exclusively—leaving other parts of the immune system or body tissues undisturbed.
“So, we tried to hunt for molecular targets in activated T-cells downstream of the TCR signal,” Chen said. “If we can delete such targets in the activated T-cells, or make activated T-cells dysfunctional, we can solve the issue of autoimmunity and transplant rejection.”
That could provide a new treatment option for organ transplant acceptance. The current therapy is medication that targets non-selective pathways to T-cells as well as other body cells. Long-term transplant survival is limited by the side effects of this medication.
Related: Lungs in a Box
By systematically deleting different molecules in T-cells, Chen’s team was able to determine which ones were necessary for the T-cells to function.
The researchers also were able to identify what Chen called the “master regulator” of T-cell function—a critical switch that controls T-cell function and dysfunction—and a pathway to target those actions.
The function controlling gene expression in T-cells is the transcription factor or messaging system called interferon regulatory factor 4, or IRF4—which is usually only found in the immune system and not expressed in other cells.
Chen said IRF4, which is only activated with the TCR signals, is what needs to be targeted to solve the problem of transplant rejection or autoimmunity issues.
“We found, on one of the molecules, IRF4, if you deleted it after the TCR signaling, the T-cells will become dysfunctional,” Chen said. “That is important and surprising, because why is it only one of the molecules downstream of TCR signaling that connects to the whole T-cell function?”
The advantage of this new method, versus the current drug therapy, is that it targets only active T-cells that were already exposed to antigens, leaving naïve T-cells—those that have never seen antigens and produce no or little IRF4—alone.
The team found that by inhibiting IRF4 expression for 30 days, the typical timeframe required for transplant patients to remain infection-free, the T-cells became irreversibly dysfunctional and did not try to attack the transplanted organ. In practice, this could mean prolonging a patient’s ability to tolerate a life-saving implant.
The team’s findings were published in the Dec. 19 issue of Immunity, a medical journal. The researchers proved the principle that inhibiting IRF4 expression is possible by identifying the signal pathways that induce the IRF4 in T-cells.
“This will be huge because it isn’t just one response that you can control,” Chen said. “I was surprised that one molecule knocked out in T-cells could, 100 percent, prevent their function. Why IRF4 is the only molecule that I have found so far that can make the functional gene switch is what we still have to figure out.”
Related: Tiny Valves for Tiny Bodies
#TalkTuesday: Avocados are one of the best sources of vitamin E. They help to reduce blood pressure and lower cholesterol levels. And they’re delicious, too! Have you added this #superfood into your diet?
.@ColonCancerDoc on new #colorectalcancer surveillance study: “These findings differ from historical data and argue to reconsider current guideline recommendations, in the U.S.” https://t.co/F844eC5ya8 #CRCSM #endcancer
Playing #guitar during #braintumor surgery helps Dr. Sujit Prabhu preserve survivor Robert Alvarez’s brain function: “Everything worked like a symphony.” #BTSM #endcancer https://t.co/kELJrAzSbz
MD Anderson Cancer CenterMDAnderson
“I knew I had pancreatic cancer,” Jane Mooney recalls. “But I chose not to know any other details, because the only way for me to remain optimistic was to keep my life very simple. I had to concentrate on the task at hand.” #endcancer
Why #prostatecancer survivor Andy Moriarty advocates for men to get annual physical and cancer screenings: https://t.co/IyuGHSWuw2 #CancerMoonshot #endcancer https://t.co/SKp1Tz4CDz
Mark your calendars now for a Geriatrics for Primary Care Providers course on June 23. Register here: https://t.co/QwSaH6KVwL https://t.co/sK8kRsRKDA
Baylor College of MedicineBaylorCollegeOfMedicine
Bumping up your weekly exercise over as little as six years could lead to a decrease in heart failure risk.
Specialty court helps Veterans get back on track https://t.co/qYxnqZRAQE via @GainesvilleSun
Two-hundred and twenty-seven McGovern Medical School students marched across the stage to receive their degrees during the school's 45th commencement ceremony on May 18. Congratulations, graduates! #UTHealth18 #ManyFacesOfUTHealth
Known for providing the highest level of care for adults & children with critical injuries, the Red Duke Trauma Institute at Memorial Hermann-Texas Medical Center is one of the busiest Level I trauma centers in the nation. Watch part two: https://t.co/K9PoJyjeGZ. #EMSWeek #TeamMH https://t.co/1WwG3Qh0D3
Researchers have synthesized and isolated plasmonic magnesium nanoparticles that show all the promise of their gold, silver and aluminum cousins with none of the drawbacks. https://t.co/vlCSeReYKN https://t.co/rYDoL5aetL
Fargo VA selected for ‘Whole Health’ initiative https://t.co/RGFuTDArDq via @inforum
Today’s #VeteranOfTheDay is @USArmy Veteran Elvis Arthur Mason. https://t.co/ij3B2SLLlk
U.S. Department of Veterans AffairsVeteransAffairs
Today’s #VeteranOfTheDay is Army Veteran Elvis Arthur Mason. Arthur served from 1942 to 1946 and 1950 to 1952. Elvis was born in October 1921 in Elberfeld, Indiana. He moved to Oakland City, Indiana and was drafted into the Army at the age of 20. Elvis completed basic training at Camp Swift, Texas and was assigned to an infantry regiment. He also completed swamp training, desert training and mountain training in Louisiana, California and West Virginia, respectively. Elvis’s unit was deployed to Europe and landed in England shortly after D-Day. Elvis traveled to France and volunteered to drive gasoline to other allied camps. His unit engaged in combat for 100 consecutive days and moved through France, Germany, Luxembourg, Belgium and Holland to push the German army back. Elvis took over as platoon leader during this campaign and credited the platoon’s camaraderie for helping the soldiers get through the difficult time. Elvis briefly remained in Europe after Germany surrendered and participated in the liberation of a poorly maintained camp of German citizens. He then returned to the United States and was preparing to travel to Japan when the Japanese surrendered in 1945. Elvis continued to serve at Camp Shelby, Mississippi and Camp Butler, North Carolina before he was honorably discharged in December, 1945. He joined the Army reserves and was called to join the Korean War in 1950. He reported to Fort Leonard Wood, Missouri in October and served in Japan and Korea, where he helped to build roads and airstrips for artillery planes. Elvis was awarded the Purple Heart and a Bronze Star. He passed away on July 14, 2012 at the age of 90. We honor his service.
Looking for a gift for your graduate to remember his or her time at Baylor College of Medicine? Check out our team shop for shirts, hats, cups, and so much more! https://t.co/QQw2ZfLPHk https://t.co/9wxEsAZxOJ