Rheumatoid arthritis (left) and psoriasis (right) are two of the disorders that may be caused by an excess of immune cells called Th-17. [Credit: David Jones, flickr.com (left); The Wednesday Island, Wikimedia (right)]
Millions of Americans know the painful, debilitating symptoms that occur as the body is attacked by a rogue immune system, causing disorders such as rheumatoid arthritis, psoriasis and graft-versus-host disease. Although these conditions may seem very different, mounting evidence points to a common culprit: a white blood cell called Th-17, whose role in the body remains controversial.
In healthy people, Th-17 helps fight infection by guarding the skin, intestine and lungs against pathogens, alerting the immune system to foreign invaders. But some studies show that having too many of these cells may lead to disease by prompting the body to attack its own healthy cells. In the hopes of combating or even preventing the disorders Th-17 may cause, researchers are now trying to quell the excessive cells.
“[Th-17] controls the borders of our body from the exterior, but if they are over-stimulated, they can damage our own tissues,” says Dan Littman, a professor of molecular immunology at New York University who has investigated Th-17 since the cells were first described in 2005.
Autoimmune diseases wreak havoc on the body when healthy tissue becomes the casualty of an immune system gone awry. The abnormal immune response ensnares normal cells, which get caught like civilians in the middle of a military invasion, says Jay Kolls, a pediatric pulmonologist at the University of Pittsburgh who researches Th-17 and its role in respiratory diseases. “There’s a lot of innocent [healthy tissue] taking damage even though it’s not involved,” says Kolls.
Overactivity of Th-17, for example, plays a sizable role in the attack on healthy cells that occurs in graft-versus-host disease, or GVHD, according to a study published in February in the journal Blood. GVHD, in which transplanted donor immune cells attack the recipient’s body, strikes between 30 and 80 percent of human marrow recipients. Although it’s not a true autoimmune disease, it involves an overactive immune system incorrectly attacking tissue, has many of the same symptoms as autoimmune diseases, and also appears to be heavily influenced by Th-17 cells.
In the Blood study, researchers injected bone marrow into mice with normal Th-17 levels. When they then gave the animals additional Th-17, the mice developed GVHD. “[Th-17 cells] appear to be able to cause a significant amount of GVHD symptoms,” says Jonathan S. Serody, co-author of the study and a hematologist and researcher at the University of North Carolina School of Medicine in Chapel Hill. “Our hope would be that you could come up with therapies specific to these cells.”
Today, treatment for autoimmune diseases and GVHD entails a cocktail of drugs to suppress the immune system. But these potentially life-saving medications can also fatally weaken the body’s ability to combat infection. “Immunosuppressants kill both the good cells that respond to infections and the bad ones that cause GVHD” and other autoimmune diseases, says Kolls. By targeting Th-17 specifically, however, it might be possible to get around suppressing the patient’s immune system so greatly.
To decrease levels of Th-17 in the body, scientists in Littman’s lab at NYU hope to deactivate the protein that tells the immune system to boost Th-17 production. This protein hibernates until a specific molecule slips into its tiny pocket like a key in a lock. Fabio Santori, a researcher working under Littman’s guidance, is trying to identify the shape of the keyhole and says that targeting Th-17 could hold potential for pharmaceutical therapies of autoimmune diseases. Santori hopes that, once scientists have identified this shape, they will be able to trick the protein into binding with the wrong molecule, thereby preventing the overproduction of Th-17 in the body. “In that case, you can treat diseases caused by Th-17 cells,” he says.
Other scientists are taking a different approach to combating Th-17: silencing the molecules that help cells communicate with each other. “We do not know how the body really coordinates its activities to make Th-17,” says Vijay Kuchroo, a neurologist and researcher at Brigham and Women’s Hospital in Boston. Solving this riddle, he says, could open the door to a drug that would block communication between cells, taming the body’s production of Th-17 and halting the self-destructive rampage.