Hunger-promoting hypothalamic neurons modulate effector and regulatory T-cell responses
| Autor: | MATARESE, GIUSEPPE, Procaccini C, Menale C, Kim JG, Kim JD, Diano S, Diano N, De Rosa V, Dietrich MO, Horvath TL, PANE, FABRIZIO |
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| Přispěvatelé: | Matarese, Giuseppe, Procaccini, C, Menale, C, Kim, Jg, Kim, Jd, Diano, S, Diano, N, De Rosa, V, Dietrich, Mo, Horvath, Tl, Pane, Fabrizio |
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Encephalomyelitis Autoimmune Experimental Hunger Regulatory T cell Hypothalamus Autoimmunity Mice Transgenic Inflammation Thymus Gland Adaptive Immunity Biology T-Lymphocytes Regulatory Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Immune system Sirtuin 1 Antigen Catalytic Domain Internal medicine medicine Animals Humans Genetic Predisposition to Disease Antigens Alleles Myelin Sheath 030304 developmental biology Mice Knockout Neurons 0303 health sciences Multidisciplinary FOXP3 Forkhead Transcription Factors Biological Sciences Flow Cytometry Acquired immune system Cell biology Endocrinology medicine.anatomical_structure biology.protein medicine.symptom Food Deprivation 030217 neurology & neurosurgery |
| Zdroj: | Proceedings of the National Academy of Sciences. 110:6193-6198 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1210644110 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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