First Author | Matarese G | Year | 2013 |
Journal | Proc Natl Acad Sci U S A | Volume | 110 |
Issue | 15 | Pages | 6193-8 |
PubMed ID | 23530205 | Mgi Jnum | J:196193 |
Mgi Id | MGI:5486649 | Doi | 10.1073/pnas.1210644110 |
Citation | Matarese G, et al. (2013) Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses. Proc Natl Acad Sci U S A 110(15):6193-8 |
abstractText | 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. |