The social side of immunity
Societies, if they are to operate smoothly, depend on specialization, cooperation and coordination. Members have individual roles to play—as doctors, lawyers, teachers, traffic cops or even immunologists—but unless they all communicate and integrate their efforts, the outcome can be chaotic and possibly disastrous.
So it is, too, with the immune system. Its overall mission of defending against infection and cancer is carried out by brigades of specialized cells that must act at the appropriate time, with appropriate vigor, in coordinated fashion. Too weak a response can open the door to illness; too strong a response may turn the body against itself, resulting in autoimmune diseases such as multiple sclerosis, lupus and rheumatoid arthritis.
Like a sociologist dissecting relationships in a particular population, Yasmina Laouar is trying to understand the interplay among various components of the immune system. And just as a social scientist might listen to conversations or examine correspondence, Laouar is studying the means of communication among her study subjects. Typically, immune system cells interact with one another through direct contact or through chemical messengers. Laouar is focusing her attention on one chemical messenger called Transforming Growth Factor beta (TGF-β), known to be a potent regulator of the immune system.
Other researchers have looked in detail at how TGF-β affects T cells, which play a central role in immunity, but Laouar is exploring the less understood interaction of TGF-β with two other cells types: natural killer (NK) cells and dendritic cells. She and coworkers in her lab do this by studying mice that are normal in every way except that their dendritic cells and NK cells have been engineered to ignore TGF-β.
Mice whose dendritic cells can’t interact with TGF-β develop a disease similar to multiple sclerosis. But the inability of both dendritic cells and NK cells to engage with TGF-β also appears to have benefits: it protects the mice from infection with a virus known as MCMV, as well as from the parasitic disease leishmaniasis. What’s more, the mice seem to have enhanced tumor-fighting abilities.
“What that means is that in normal situations, TGF-β is helpful for preventing autoimmunity, but in certain circumstances, you may get a better response to parasites, viruses and tumors without it,” says Laouar. This is important to know, not only for understanding how the immune system normally works, but also for designing more effective treatments and preventive strategies against infectious diseases and cancer. Already, dendritic cells are used in cancer vaccines, and NK cells have been enlisted for cancer treatment.
“Our work suggests that in the future, it may be possible to engineer dendritic cells and NK cells to make them more potent or less potent,” says Laouar, “which could really make a difference in the efficacy of therapy.”
