Targeting the GM-CSF receptor for the treatment of CNS autoimmunity

Igal Ifergan, Todd S. Davidson, Hania Kebir, Dan Xu, Daphne Palacios-Macapagal, Jennifer Cann, Jane M. Rodgers, Zoe N. Hunter, Camille L. Pittet, Sara Beddow, Clare A. Jones, Alexandre Prat, Matthew A. Sleeman, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

In multiple sclerosis (MS), there is a growing interest in inhibiting the pro-inflammatory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to evaluate the therapeutic potential and underlying mechanisms of GM-CSF receptor alpha (Rα) blockade in animal models of MS. We show that GM-CSF signaling inhibition at peak of chronic experimental autoimmune encephalomyelitis (EAE) results in amelioration of disease progression. Similarly, GM-CSF Rα blockade in relapsing-remitting (RR)-EAE model prevented disease relapses and inhibited T cell responses specific for both the inducing and spread myelin peptides, while reducing activation of mDCs and inflammatory monocytes. In situ immunostaining of lesions from human secondary progressive MS (SPMS), but not primary progressive MS patients shows extensive recruitment of GM-CSF Rα+ myeloid cells. Collectively, this study reveals a pivotal role of GM-CSF in disease relapses and the benefit of GM-CSF Rα blockade as a potential novel therapeutic approach for treatment of RRMS and SPMS.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalJournal of Autoimmunity
Volume84
DOIs
StatePublished - Nov 2017

Keywords

  • Dendritic cells
  • EAE
  • GM-CSF
  • Inflammatory monocytes
  • MS
  • Multiple sclerosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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