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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.