Stress Damages Immune System

Researchers have identified the molecular mechanism that causes the immune system to function less effectively when an individual is under physical or mental stress.

Investigators at the Garvan Institute of Medical Research (Darlinghurst, AU) focused their attention on neuropeptide Y (NPY), a 36–amino acid peptide made by neurons throughout the brain and by other secretory cells of the body. NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy.

The investigators worked with a line of mice that had been genetically engineered to lack the gene for production of NPY. They showed that T cells from NPY-deficient mice were hyper-responsive to activation and triggered severe colitis after transfer into lymphopenic mice. These findings implied that signaling through an NPY receptor on T cells inhibited T cell activation and controlled the magnitude of T cell responses. Strangely enough, the NPY-deficient mice were resistant to T helper type 1 (Th1) cell-mediated inflammatory responses and showed reduced levels of the Th1 cell-promoting cytokine interleukin 12 and reduced interferon gamma production.

This shortcoming was due to functionally impaired antigen-presenting cells (APCs), and consequently, NPY-deficient mice had reduced numbers of effector T cells. These results, which were published in the December 5, 2005, issue of the Journal of Experimental Medicine, demonstrated a fundamental bimodal role for the NPY receptor in the immune system, serving as a strong negative regulator on T cells as well as a key activator of APC function.

Senior author Dr. Fabienne Mackay, associate professor of medicine at the Garvan Institute of Medical Research, said, "Under normal conditions, circulating immune cells produce small amounts of NPY, which enables the immune cells on sentry duty and the TH1 immune cells to operate--it is a yin and yang kind of situation. But too much NPY means that the TH1 attack is prevented despite the foreign invaders being identified--and this is what happens during stress.”



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Garvan Institute for Medical Research