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


ABSTRACT: 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.

SUBMITTER: Matarese G 

PROVIDER: S-EPMC3625304 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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

Matarese Giuseppe G   Procaccini Claudio C   Menale Ciro C   Kim Jae Geun JG   Kim Jung Dae JD   Diano Sabrina S   Diano Nadia N   De Rosa Veronica V   Dietrich Marcelo O MO   Horvath Tamas L TL  

Proceedings of the National Academy of Sciences of the United States of America 20130325 15


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 associa  ...[more]

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