Leptin, metabolic state and natural regulatory T cells: cellular and molecular basis for a novel immune intervention in autoimmunity

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 Foxp3+CD4+CD25+ 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.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• natural sciences biological sciences biochemistry biomolecules proteins
• medical and health sciences basic medicine neurology multiple sclerosis

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

• autoimmunity
• immune response
• inflammation
• leptin
• metabolism
• multiple sclerosis
• nutritional state
• regulatory T cells

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• 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)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

ERC-2007-StG
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-SG - ERC Starting Grant

Host institution

Beneficiaries (1)