A recently identified gene allows immune cells to start the self-destructive processes thought to underlie autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis, School of Medicine researchers have found.
Researchers showed that mice without the Batf gene lacked a type of inflammatory immune cell and were resistant to a procedure that normally induces an autoimmune condition similar to human MS. They plan to look for other genes and proteins influenced by Batf that could be targets for new treatments for autoimmune diseases.
“Batf allows immune cells to head down a pathway that’s been a very hot topic in immunology because of its potential links to autoimmune disease,” said senior author Kenneth Murphy, M.D., Ph.D., professor of pathology and immunology and a Howard Hughes Medical Institute investigator. “We showed that Batf regulates the only other gene previously revealed to control this pathway, so Batf may have quite a bit to teach us about autoimmunity.”
The findings appeared in a recent issue of Nature.
Lead author Barbara Schraml, Ph.D., a former graduate student, found that the loss of Batf affected immune cells known as T cells. Normally T cells take on specialized roles, becoming cells that promote various defensive responses or that recruit inflammatory cells to sites of infection. In mice without Batf, though, one of those roles was blocked: the mice had no inflammatory Th17 cells.
Murphy and other researchers first identified the Th17 pathway four years ago. While such cells help defend the body from bacterial infections, scientists have found that IL17, an inflammatory compound made by Th17 cells, is frequently present at sites of active autoimmune disease.
Batf is a transcription factor, which means that the protein made from the gene acts to turn the production of proteins from other genes on and off. Its only previously identified role was as a partner with another common transcription factor.
Schraml showed that Batf had to be present for Th17 cells to make ROR-gamma-T, the only other gene known to force T cells to become Th17 cells. She also found that the presence of Batf made it possible for T cells to make more IL17.