title: 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.
authors.affiliation: Dipartimento di Medicina e Chirurgia, Università degli Studi di Salerno, 84081 Salerno, Italy. gmatarese@unisa.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
authors.forename: Claudio
authors.initials: C
authors.lastname: Procaccini
authors.forename: Ciro
authors.initials: C
authors.lastname: Menale
authors.forename: Jae Geun
authors.initials: JG
authors.lastname: Kim
authors.forename: Jung Dae
authors.initials: JD
authors.lastname: Kim
authors.forename: Sabrina
authors.initials: S
authors.lastname: Diano
authors.forename: Nadia
authors.initials: N
authors.lastname: Diano
authors.forename: Veronica
authors.initials: V
authors.lastname: De Rosa
authors.forename: Marcelo O
authors.initials: MO
authors.lastname: Dietrich
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
mesh_terms: D056704:Adaptive Immunity; D000483:Alleles; D000818:Animals; D000941:Antigens / Q000378:metabolism; D015551:Autoimmunity; D020134:Catalytic Domain; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism; D005434:Flow Cytometry; D005508:Food Deprivation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D006815:Hunger; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D056564:Sirtuin 1 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D013950:Thymus Gland / Q000378:metabolism
chemical_list: D000941:Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D056564:Sirtuin 1