Rapamycin inhibits relapsing experimental autoimmune encephalomyelitis by both effector and regulatory T cells modulation

Marianna Esposito, Francesca Ruffini, Matteo Bellone, Nicola Gagliani, Manuela Battaglia, Gianvito Martino, Roberto Furlan

Research output: Contribution to journalArticlepeer-review

Abstract

Rapamycin is an oral immunosuppressant drug previously reported to efficiently induce naturally occurring CD4 +CD25 +FoxP3 + regulatory T ( nT reg) cells re-establishing long-term immune self-tolerance in autoimmune diseases. We investigated the effect of rapamycin administration to SJL/j mice affected by PLP 139-151-induced relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE). We found that oral or intraperitoneal treatment at the peak of disease or at the end of the first clinical attack, dramatically ameliorated the clinical course of RR-EAE. Treatment suspension resulted in early reappearance of disease. Clinical response was associated with reduced central nervous system demyelination and axonal loss. Rapamycin induced suppression of IFN-γ, and IL-17 release from antigen-specific T cells in peripheral lymphoid organs. While CD4 +FoxP3 + cells were unaffected, we observed disappearance of CD4 +CD45RB high effector T (T eff) cells and selective expansion of T reg cells bearing the CD4 +CD45RB lowFoxP3 +CD25 +CD10 3 + extended phenotype. Finally, the dual action of rapamycin on both T eff and T reg cells resulted in modulation of their ratio that closely paralleled disease course. Our data show that rapamycin inhibits RR-EAE, provide evidence for the immunological mechanisms, and indicate this compound as a potential candidate for the treatment of multiple sclerosis.

Original languageEnglish
Pages (from-to)52-63
Number of pages12
JournalJournal of Neuroimmunology
Volume220
Issue number1-2
DOIs
Publication statusPublished - Mar 30 2010

Keywords

  • EAE
  • FoxP3
  • Multiple sclerosis
  • Rapamycin
  • T regulatory cells

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

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