Neurons Govern Immunity

Hunger-associated molecules in the hypothalamus suppress inflammation.

Kate Yandell
Oct 31, 2013

MULTITASKING: The protein Sirt1 can promote hunger and also tamp down autoimmune responses.© 3DCiencia


The paper
G. Matarese et al., “Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses,” PNAS, 110:6193-98, 2013.

The finding
Sirtuins are proteins that promote hunger when expressed by the Agouti-related peptide-expressing (AgRP) neurons in the hypothalamus. Sirtuins also prevent inflammation and keep CD4+ T cells from becoming overactive, but it has been unclear where in the body the sirtuins act to modulate immune function. Tamas Horvath of Yale University School of Medicine and colleagues found that knocking out Sirt1 in the AgRP neurons in mice increased peripheral CD4+ T-cell proliferation, suggesting a link between nutrition and immune response.

The experiments
Mice lacking Sirt1 in their AgRP neurons not only had more CD4+ T cells, they also had fewer regulatory T cells (Tregs), which help prevent autoimmunity. The Tregs that were present in the Sirt1-knockout mice produced fewer anti-inflammatory cytokines than in wild type mice. And a mouse model of an autoimmune disease that also lacked Sirt1 had more pronounced autoimmune reactions than mice with the protein.

The significance
The study showed an “unexpected link between hypothalamic gene regulation and immune cell function,” writes Matthew Hirschey, of Duke University, in an e-mail. Horvath hypothesizes that food could influence the immune system through sirtuins, such that a low-nutrient diet would increase Sirt1 levels and decrease inflammation, while a glut of nutrients would send Sirt1 levels diving, provoking an inflammatory response. “The less hungry you are the more active your immune system is in the periphery,” Horvath says.

The application
Horvath hopes to test the effects of fasting and feasting on the immune system in mice and humans, to see if maintaining a state of hunger could suppress inappropriate autoimmunity, and whether eating could stimulate the immune system in the infection-prone.