Interleukin-11 potentiates oligodendrocyte survival and maturation, and myelin formation

Yueting Zhang, Carla Taveggia, Carmen Melendez-Vasquez, Steven Einheber, Cedric S. Raine, James L. Salzer, Celia F. Brosnan, Gareth R. John

Research output: Contribution to journalArticlepeer-review

Abstract

Mechanisms that regulate oligodendrocyte survival and myelin formation are an intense focus of research into myelin repair in the lesions of multiple sclerosis (MS). Although demyelination and oligodendrocyte loss are pathological hallmarks of the disease, increased oligodendrocyte numbers and remyelination are frequently observed in early lesions, but these diminish as the disease course progresses. In the current study, we used a microarray-based approach to investigate genes regulating repair in MS lesions, and identified interleukin-11 (IL-11) as an astrocyte-derived factor that potentiates oligodendrocyte survival and maturation, and myelin formation. IL-11 was induced in human astrocyte cultures by the cytokines IL-1β and TGFβ1, which are both prominently expressed in MS plaques. In MS tissue samples, IL-11 was expressed by reactive astrocytes, with expression particularly localized at the myelinated border of both active and silent lesions. Its receptor, IL-11Rα, was expressed by oligodendrocytes. In experiments in human cultures in vitro, IL-11Rα localized to immature oligodendrocytes, and its expression decreased during maturation. In cultures treated with IL-11, we observed a significant increase in oligodendrocyte number, and this was associated with enhanced oligodendrocyte survival and maturation. Importantly, we also found that IL-11 treatment was associated with significantly increased myelin formation in rodent CNS cocultures. These data are the first to implicate IL-11 in oligodendrocyte viability, maturation, and myelination. We suggest that this pathway may represent a potential therapeutic target for oligodendrocyte protection and remyelination in MS.

Original languageEnglish
Pages (from-to)12174-12185
Number of pages12
JournalJournal of Neuroscience
Volume26
Issue number47
DOIs
Publication statusPublished - Nov 22 2006

Keywords

  • Astrocyte
  • Cytokine
  • Multiple sclerosis
  • Myelin
  • Oligodendrocyte
  • Repair

ASJC Scopus subject areas

  • Neuroscience(all)

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