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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.
- Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.15 pp. 6193-6198
- CD4-positive T-lymphocytes, adaptive immunity, autoimmune diseases, cytokines, delayed hypersensitivity, disease resistance, energy, energy metabolism, hypothalamus, mice, neurons, sympathetic nervous system
- 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.