Two-thirds to three-quarters of the estimated 700,000 Americans living with Crohn’s disease, an autoimmune condition that can disrupt the entire gastrointestinal tract, will require surgery at some point during their lives. Patients and physicians often turn to this surgical intervention after a patient develops resistance to current treatments, such as steroids. Now scientists from the Florida campus of The Scripps Research Institute (TSRI) have identified a normally small subset of immune cells that may play a major role in the development of Crohn’s disease generally and in disease-associated steroid resistance specifically. The study, published online January 6, 2014 in the Journal of Experimental Medicine, focused on Th17 cells, part of a family of white blood cells that have been implicated in numerous autoimmune diseases, including Crohn’s disease. In the new study, the researchers found that a subset of TH17 cells in humans expresses the multidrug transporter MDR1 and that these cells are linked to inflammation in Crohn’s patients. MDR1—a protein famous for promoting drug-resistance in tumors—may also act as a survival and steroid resistance factor in T cells, particularly in harsh environments such as the inflamed gut mucosa of Crohn’s disease patients. “Our study is the first to identify and characterize this uniquely pro-inflammatory T-cell subset,” said biologist Dr. Mark Sundrud, a TSRI assistant professor who led the study. “We were able to sort these cells directly out of damaged tissue resected from Crohn’s patients and found that these pro-inflammatory cells are over-expressing genes that contribute to disease.” Within healthy individuals, only approximately 5 to 10 percent of CD4+ T cells are MDR1-expressing TH17 cells.
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