“It’s clear that immune-mediated responses are key to diseases not previously associated with the immune system,” says Arlene Sharpe ’82, the George Fabyan Professor of Comparative Pathology at HMS. Reunion Week’s faculty symposium, held May 29, presented some discoveries that are illuminating the role that chronic inflammation plays in cancers, allergies, inflammatory bowel disease, neurodegenerative diseases such as multiple sclerosis, and metabolic diseases such as diabetes.
There’s been a troubling rise in obesity over the past 20 years, which, according to the panelists, has paralleled increases in cardiac and metabolic diseases and in type 2 diabetes. Diane Mathis, the Morton Grove-Rasmussen Professor of Immunohematology at HMS, notes that chronic low-grade inflammation underlies these diseases. She spoke in particular about the inflammatory aspects of obesity. Her lab found that regulatory T cells, which help control almost all immune responses, are missing in the adipose tissue of an obese person. “We have found a factor that helps regulatory T cells establish themselves,” says Mathis, adding that increasing this factor in people who are obese may help them avoid the chronic conditions associated with obesity.
Recent research has also unraveled some of the mysteries of inflammatory bowel disease, reports Ramnik Xavier, the Kurt J. Isselbacher Professor of Medicine in the Field of Gastroenterology at HMS and chief of the gastroenterology unit at Massachusetts General Hospital. Scientists now know the genetic factors that contribute to the disease and the important role that gut bacteria play. “Many of the genes associated with Crohn’s,” says Xavier, “are responsible for the immune system’s recognition of microbes.” His lab found that Crohn’s disease and ulcerative colitis have microbial “signatures”—a balance of “good” and “bad” bacteria that are condition-specific—that also indicate disease severity.
After a century of unfulfilled promises, “I think immunotherapy is ready to change the face of cancer therapy,” says Gordon Freeman, an HMS associate professor of medicine at Dana-Farber Cancer Institute. Stimulating immune response hasn’t worked, but blocking inhibiting pathways has. His lab discovered two interacting protein molecules that affect T-cell function, and found that cancer cells “learned” to express the protein that inhibits immune response. Treatments that used antibodies to that protein decreased tumor size and stopped tumor growth for years.
Vijay Kuchroo, the Samuel L. Wasserstrom Professor of Neurology at HMS, studies autoimmunity and tissue inflammation and discovered TH17, a pathogenic T cell. TH17 is present in inflamed tissue, including in multiple sclerosis lesions in the brain. A clinical trial of an anti-TH17 drug showed a significant decrease in the number of MS lesions in the brain. His research team also found cytokines that make T cells pathogenetic. Kuchroo’s group also has investigated salt’s effect on the immune system and its role in inflammatory bowel disease.
A video of the symposium may be viewed at hms.harvard.edu/reunion/2014-recap.
Image: Suzanne Camarata Photography