New York, NY—April 21, 2015
Researchers at Hospital for Special Surgery have identified a potential new drug target for treating patients with autoimmune diseases, such as lupus or rheumatoid arthritis. The research, which appears in the April issue of the journal Immunity, shows that depleting so-called dendritic cells, can decrease an immune response.
“We have discovered a new way to disrupt an ongoing immune response,” said lead author Theresa Lu, MD, PhD, an associate scientist in the Autoimmunity and Inflammation Program and Pediatric Rheumatology at Hospital for Special Surgery in New York City.
In autoimmune diseases such as lupus or rheumatoid arthritis, immune cells including B cells and T cells, which normally protect the body from outside invaders, run amok and attack parts of the body instead. For years, researchers have been working to figure out a way to turn off inappropriate immune responses.
"B cells and T cells become activated and multiply in lymphoid tissues such as the lymph nodes or spleen," explained Dr. Lu. "We have been studying these lymph nodes, which are somewhat like the homes in which the B cells and T cells live."
Previous studies have shown that within the lymph nodes, so-called stromal reticular cells supply survival factors or proteins that help T cells and B cells thrive. "If we can understand how these reticular cells survive during immune responses, then we can try to get rid of them to disrupt the immune response," said Dr. Lu. The researchers began to focus their attention on dendritic cells that are known to sit next to the stromal reticular cells. "The thought was that maybe the dendritic cells were helping the reticular cells survive," said Dr. Lu.
To find out whether this was true, the researchers used transgenic mice that were designed to be deficient in dendritic cells and found that when dendritic cells started to die, the reticular cells started to die off too. “We found that when the dendritic cells and reticular cells died off, the lymphocytes also died off as a downstream effect,” said Dr. Lu.
The findings suggest that drugs that can kill off dendritic cells might have a therapeutic effect in patients with autoimmune diseases. "You could potentially use these drugs to get patients through the worst part of their disease and decrease the amount of steroids that patients with lupus take," said Dr. Lu. She pointed out that there are drugs already on the market that can kill dendritic cells. The researchers plan to test these drugs in mouse models of lupus and other autoimmune diseases.
Other authors of the study, "A Dendritic Cell-stromal Axis Maintains Immune Responses in Lymph Nodes," are Varsha Kumar, Dragos Dasoveanu, Susan Chyou, Te-Chen Tzeng, Cristina Rozo from HSS; William Stohl, MD, PhD, from the University of Southern California; Yong Liang and Yang-Xin Fu, MD, PhD, from the University of Chicago; and Nancy Ruddle, PhD, from the Yale School of Public Health.