Leptin increase in multiple sclerosis associates with reduced number of CD4+CD25+ regulatory T cells

Giuseppe Matarese, Pietro Biagio Carrieri, Antonio La Cava, Francesco Perna, Veronica Sanna, Veronica De Rosa, Daniela Aufiero, Silvia Fontana, Serafino Zappacosta

Research output: Contribution to journalArticle

Abstract

We analyzed the serum and cerebrospinal fluid (CSF) leptin secretion and the interaction between serum leptin and CD4+CD25+ regulatory T cells (TRegs) in naïve-to-therapy relapsing-remitting multiple sclerosis (RRMS) patients. Leptin production was significantly increased in both serum and CSF of RRMS patients and correlated with IFN-γ secretion in the CSF. T cell lines against human myelin basic protein (hMBP) produced immunoreactive leptin and up-regulated 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 in response to hMBP. Interestingly, in the RRMS patients, an inverse correlation between serum leptin and percentage of circulating T Regs was also observed. To better analyze the finding, we enumerated TRegs in leptin-deficient (ob/ob) and leptin-receptor-deficient (db/db) mice and observed the significant increase in TRegs. Moreover, treatment of WT mice with soluble ObR fusion protein (ObR:Fc) increased the percentage of TRegs and ameliorated the clinical course and progression of disease in proteolipid protein peptide (PLP 139-151)-induced relapsing-experimental autoimmune encephalomyelitis (R-EAE), an animal model of RRMS. These findings show an inverse relationship between leptin secretion and the frequency of TRegs in RRMS and may have implications for the pathogenesis of and therapy for multiple sclerosis.

Original languageEnglish
Pages (from-to)5150-5155
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number14
DOIs
Publication statusPublished - Apr 5 2005

Keywords

  • Autoimmunity
  • Hormones
  • Metabolism
  • Tolerance

ASJC Scopus subject areas

  • Genetics
  • General

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