LEPTINMS
"Leptin, metabolic state and natural regulatory T cells: cellular and molecular basis for a novel immune intervention in autoimmunity"
| Coordinatore | CONSIGLIO NAZIONALE DELLE RICERCHE
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | Italy [IT] |
| Totale costo | 880˙000 € |
| EC contributo | 880˙000 € |
| Programma | FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | ERC-2007-StG |
| Funding Scheme | ERC-SG |
| Anno di inizio | 2008 |
| Periodo (anno-mese-giorno) | 2008-07-01 - 2011-10-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
CONSIGLIO NAZIONALE DELLE RICERCHE
Organization address
address: Piazzale Aldo Moro 7 contact info |
IT (ROMA) | hostInstitution | 0.00 |
| 2 |
CONSIGLIO NAZIONALE DELLE RICERCHE
Organization address
address: Piazzale Aldo Moro 7 contact info |
IT (ROMA) | hostInstitution | 0.00 |
Mappa
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Obiettivo del progetto (Objective)
'Our Group has been investigating the cellular and molecular mechanisms involving leptin, the adipocyte-derived hormone, in the pathogenesis of autoimmunity such as experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS).We analyzed the serum and cerebro-spinal fluid (CSF) leptin secretion and the interaction between serum leptin and naturally occurring Foxp3CD4CD25 regulatory T cells (Tregs) in naïve-to-therapy multiple sclerosis (MS) patients. Leptin production was significantly increased in serum and CSF of MS patients and correlated with interferon-gamma (IFN-g) secretion in the CSF.T cell lines against human myelin basic protein (hMBP) produced leptin and upregulated the expression of the leptin receptor (ObR) after activation with hMBP; treatment with either anti-leptin or anti-leptin receptor neutralizing antibodies inhibited in vitro proliferation to hMBP.Interestingly, in the MS patients an inverse correlation between serum leptin and percentage of circulating Tregs was also observed. Moreover, treatment of EAE-susceptible mice with a leptin antagonist increased the percentage of Tregs and ameliorated disease clinical course and progression in proteolipid protein peptide (PLP139-151)-induced EAE.These findings show for the first time an inverse relationship between leptin secretion and the frequency of Tregs in EAE and MS.In the present project, we intend to analyze in vitro and in vivo, the relationship between leptin and Tregs in human and in animal models, studying at molecular and cellular level the effect of leptin and its neutralization on the survival, proliferation and cytokine secretion of Tregs.Despite recent advances, the precise requirements for the physiological development of Tregs such as the necessary milieu and their molecular/biochemical requirements, remain enigmatic.Understanding these events will be important for the generation of Tregs which could have potential implications for treatment of autoimmunity.'