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 journalArticle

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

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Sirtuin 1
Hunger
Disease Susceptibility
Sympathetic Nervous System
Delayed Hypersensitivity
Adaptive Immunity
Regulatory T-Lymphocytes
Energy Metabolism
Hypothalamus
Autoimmune Diseases
Cues
Cytokines
T-Lymphocytes
Neurons
Peptides
Dasyproctidae

Keywords

  • Immune system
  • Sirtuins

ASJC Scopus subject areas

  • General

Cite this

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

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 15, 09.04.2013, p. 6193-6198.

Research output: Contribution to journalArticle

Matarese, G, Procaccini, C, Menale, C, Kim, JG, Kim, JD, Diano, S, Diano, N, De Rosa, V, Dietrich, MO & Horvath, TL 2013, 'Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses', Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 15, pp. 6193-6198. https://doi.org/10.1073/pnas.1210644110
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. / Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 15. pp. 6193-6198.
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