The functional outcome of GM-CSF in the central nervous system

Granulocyte-macrophage colony stimulating factor (GM-CSF) plays multiple roles in the development, maintenance and regulation of the immune system (Hamilton, 2008).In experimental autoimmune encephalomyelitis (EAE); an animal model of multiple sclerosis (Matyszak et al., 1999) loss of GM-CSF expression by CNS antigen-specific Th1/17 T cells abolishes their encephalitogenic potential – an effect attributed to the inability of GM-CSF-/- T cells to activate myeloid cells within the CNS. These data demonstrate GM-CSF expression by infiltrating T cells plays a critical, non-redundant role in disease induction (McQualter et al .2001), but the mechanisms involved remain poorly understood. To address this question we performed an RNAseq study to map out structural and transcriptional responses to GM-CSF in myelinating cultures derived from embryonic mouse spinal cord (Thomson et al., 2006; 2008; Sorensen et al., 2008). This revealed GM-CSF has no effect on myelin or axons in this culture system, but induced marked changes in microglia morphology and selectively upregulated microglial associated transcripts, in particular macrophage galactose N-acetyl-galactosamine specific lectin 2 (Mgl2). Mgl2/Cd301b is a type II C-type lectin that mediates recognition and phagocytosis of galactosylated structures in other tissues (Denda-Nengai et al., 2010). We speculate GM-CSF mediated induction of Mgl2 promotes phagocytosis of myelin debris