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

Giuseppe Matarese, Claudio Procaccini, Ciro Menale, Jae Geun Kim, Jung Dae Kim, Sabrina Diano, Nadia Diano, Veronica De Rosa, Marcelo O. Dietrich, Tamas L. Horvath

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)6193-6198
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number15
DOIs
Publication statusPublished - Apr 9 2013

Keywords

  • Immune system
  • Sirtuins

ASJC Scopus subject areas

  • General

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