Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses

作者：Matarese Giuseppe^*; Procaccini Claudio; Menale Ciro; Kim Jae Geun; Kim Jung Dae; Diano Sabrina; Diano Nadia; De Rosa Veronica; Dietrich Marcelo O; Horvath Tamas L

来源：Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(15): 6193-6198.

DOI：10.1073/pnas.1210644110

• immune system
• sirtuins

Whole-body energy metabolism is regulated by the hypothalamus and has an impact on diverse tissue functions. Here we show that selective knockdown of Sirtuin 1 Sirt1 in hypothalamic Agouti-related peptide-expressing neurons, which renders these cells less responsive to cues of low energy availability, significantly promotes CD4(+) T-cell activation by increasing production of T helper 1 and 17 proinflammatory cytokines via mediation of the sympathetic nervous system. These phenomena were associated with an impaired thymic generation of forkhead box P3 (FoxP3(+)) naturally occurring regulatory T cells and their reduced suppressive capacity in the periphery, which resulted in increased delayed-type hypersensitivity responses and autoimmune disease susceptibility in mice. These observations unmask a previously unsuspected role of hypothalamic feeding circuits in the regulation of adaptive immune response.

• 出版日期2013-4-9