A hormone secreted during psychological stress that interferes with immune defenses has recently been found. Researchers will examine in mice how this relationship works at a molecular level and explore whether it may play a role in autoimmune diseases, inflammatory diseases, or possibly even schizophrenia.
The investigators have discovered that a neuropeptide (called neuropeptide Y, or “NPY”), a hormone secreted during psychological stress, interferes with immune defenses. Through a receptor that it binds to, called “Y1,” it suppresses immune responses in two ways. First, Y1 receptor signaling inhibits responses by “innate” immune sentries. These are the body’s first line defenders, which recognize an invader and summon “adaptive” immune cells to attack. Second, Y1 receptor signaling suppresses activation of these adaptive immune lymphocytes. This finding links the hormone and its receptor with immune suppression. Although NPY and its Y1 receptor are not produced in the immune system, they may play an immune regulatory role that is as important as that of conventional immune factors.
Now, using animal models, the researchers will see what other immune functions the NPY/Y receptor system, and a related peptide, called “PYY,” may control. They will assess how these newly discovered immune functions fit with known processes of immune regulation. Additionally, they will explore whether malfunctions in these regulatory processes may be related to immune cell destruction of the body’s own tissues as occurs in autoimmune diseases (in which immune cells errantly attack the body’s own tissues), or in inflammatory diseases.
Significance: The discovery of a molecular link between stress and immune suppression opens up new avenues for exploring the role of stress in diseases in which immune responses are inadequate. It also suggests the possibility of developing therapeutic approaches, outside the immune system, for suppressing immune attacks against the body’s own tissues that occur in autoimmune diseases.