期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 15, 页码 6193-6198出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1210644110
关键词
immune system; sirtuins
资金
- European Union
- European Research Council [310496]
- Telethon-Juvenile Diabetes Research Foundation [GJT08004]
- Fondi per la Ricerca di Base Medical Research in Italy [RBNE08HWLZ]
- Ministero della Salute Grant [GR-2010-2315414]
- National Institutes of Health [DP1DK006850, DK080000]
- European Research Council (ERC) [310496] Funding Source: European Research Council (ERC)
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.
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