Leptin neutralization interferes with pathogenic T cell autoreactivity in autoimmune encephalomyelitis

Veronica De Rosa, Claudio Procaccini, Antonio La Cava, Paolo Chieffi, Giovanni Francesco Nicoletti, Silvia Fontana, Serafino Zappacosta, Giuseppe Matarese

Research output: Contribution to journalArticlepeer-review

Abstract

Recent evidence has indicated that leptin, an adipocyte-secreted hormone belonging to the helical cytokine family, significantly influences immune and autoimmune responses. We investigate here the mechanisms by which in vivo abrogation of leptin effects protects SJL/J mice from proteolipid protein peptide PLP 139-151-induced EAE, an animal model of MS. Blockade of leptin with anti-leptin Abs or with a soluble mouse leptin receptor chimera (ObR:Fc), either before or after onset of EAE, improved clinical score, slowed disease progression, reduced disease relapses, inhibited PLP 139-151- specific T cell proliferation, and switched cytokine secretion toward a Th2/regulatory profile. This was also confirmed by induction of forkhead box p3 (Foxp3) expression in CD4 + T cells in leptin-neutralized mice. Importantly, anti-leptin treatment induced a failure to downmodulate the cyclin-dependent kinase inhibitor p27 (p27 Kip-1) in autoreactive CD4 + T cells. These effects were associated with increased tyrosine phosphorylation of both ERK1/2 and STAT6. Taken together, our data provide what we believe is a new molecular basis for leptin antagonism in EAE and envision novel strategies of leptin-based molecular targeting in the disease.

Original languageEnglish
Pages (from-to)447-455
Number of pages9
JournalJournal of Clinical Investigation
Volume116
Issue number2
DOIs
Publication statusPublished - Feb 1 2006

ASJC Scopus subject areas

  • Medicine(all)

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