The research Wayne M. Yokoyama, MD, has done on a type of immune cells that help control early stage infections, called natural killer cells, or NK cells, has led to surprising discoveries in the field of juvenile arthritis.
It also has earned him unexpected accolades – most recently, the Arthritis Foundation’s 2010 Lee C. Howley Sr. Prize, an annual award given to scientists whose contributions open doors to new ways of understanding, treating and preventing the more than 100 forms of arthritis and related conditions. The prize pays tribute to Lee C. Howley Sr., the former chairman of Revco D.S. Inc., who helped establish the Revco Arthritis Research Center at Case Western Reserve University in Cleveland, Ohio.
John Atkinson, MD, director of Washington University’s Division of Rheumatology nominated Dr. Yokoyama for the prize because of his pioneering research into NK cells.
“He is the No. 1 person in the world in this area,” Dr. Atkinson says.
Dr. Yokoyama currently holds the Sam J. and Audrey Loew Levin Chair for Research in Arthritis at Washington University and is director of the combined MD-PhD dual-degree program there.
Honored to have received the award, Dr. Yokoyama says, “I don’t think we realized what we were going to find when we first got started in studying NK cells, but that’s sort of the point. You don’t know where the breaks are going to come from. You have to use insight and intuition to go after these findings and then it turns out a whole new field is uncovered.”
Answering the Questions
First recognized for their cancer-cell-killing qualities, NK cells exist in the immune system. But unlike other components of the immune system, which protect you only from microorganisms that you’ve previously been exposed to, NK cells do not require previous exposure. They identify virally infected cells in the body and kill them, controlling infection. But nobody understood how this happened and why NK cells didn’t kill healthy cells until Dr. Yokoyama answered those questions.
He discovered some receptors – proteins embedded in cells – that inhibit and others that activate NK cells to kill infected cells while sparing healthy cells.
“Natural killer cells were first described and discovered as killing cancer cells. So what do natural killer cells have to do with arthritis? Based on the knowledge at the time we started, the answer was probably ‘nothing,’ ” Dr. Yokoyama explains. “However, it’s now thought that natural killer cells are abnormal in patients that have certain types of juvenile idiopathic arthritis.”
Researchers don’t yet know why some juvenile idiopathic arthritis, or JIA, patients have defective NK cells, Dr. Yokoyama says. NK cells in people with JRA risk factors might somehow be inhibited from controlling infections, he says.
Exploring the Possibilities
Dr. Yokoyama, who’s been elected to the National Academy of Sciences and the American Academy of Arts and Sciences in recognition of his research, is careful not to overpromise what his discoveries might mean for people with arthritis. But because NK cells get rid of viruses, Dr. Atkinson says many researchers are eager to see how they will play out in other diseases, such as lupus and rheumatoid arthritis.
“The basic science is so impressive that it sort of overwhelmed any immediate application,” Dr. Atkinson says. “One of the theories is that these NK cells are responsible for some of the damage we see in an infected joint or lupus kidney or psoriatic skin or rheumatoid joint,” he continues. “I envision blocking NK cells to prevent damage we see in a joint.”
Since he’s shown that receptors both block and activate NK cells, Dr. Yokoyama hopes he’s giving researchers more options – to either figure out what’s stimulating NK cells and stop it, or work to enhance the receptor’s inhibitory signal. He’s thrilled that investigators around the world are now looking at these cells and receptors to see what role they play in a variety of diseases and conditions.
“By understanding how NK cells work, we can apply this knowledge to other cells in the immune system,” he says. “In that sense it’s farther reaching than just how NK cells themselves work. If it’s a concept that applies to other immune cells and gives drug companies strategies to affect the immune response then that’s good.”
Dr. Yokoyama says he’s not done searching for answers either. “I’m not ready to retire. Far from it,” he says. “I’m a scientist. There’s always something more to discover.”