Table 1.

Multiple Sclerosis: evidence for a LIF/IL-6 axis in MS pathogenesis

EVIDENCE FOR TH17 / IL17 / IL-6 ACTIVITY IN MS
(i)	The immune and neurotoxic effects of IL17 towards NG2+ glia provide crucial links the inflammatory and neurodegenerative aspects of MS.
	KANG ET AL 2013 [31]
(ii)	Infiltrating IL-17+ T cells are associated with active human disease.
	TZARTOS ET AL 2008 [45]
(iii)	In vitro treatment of CD4+ T cells from MS patients with LIF boosts Treg
	JANSSENS ET AL 2014 [46]
(iv)	BBB-endothelial cells (BBB-EC) IL-17 receptors in MS lesions; IL17 disrupts BBB tight junctions; TH17 cells transmigrate across BBB-ECs and promote CNS inflammation through CD4+ lymphocyte recruitment.
	KEBIR ET AL 2007 [47]
(v)	EAE model: increased Treg : TH17 ratio correlates with recovery of acute EAE.
	ALMONDA ET AL 2011 [48]
(vi)	EAE model: soluble LIF opposes TH17 immunity, reduces disease severity.
	CAO ET AL 2012 [33]
(vii)	IL-6:
	• TH17 immunity requires IL-6. BETTELLI ET AL 2010 [49] • EAE requires IL-6 but IL-6-null mouse that is resistant to EAE becomes sensitive to EAE if supplemented with exogenous IL-6. OKUDA ET AL 1999 [50] • EAE: site-specific IL-6 focuses inflammatory immunity in CNS QUINTANA ET AL 2009 [51]
MYELINATION
(i)	EAE model: CNS-targeted LIF limits autoimmune-mediated demyelination.
	SLAETS ET AL 2010 [53]
(ii)	Demyelination model: delivery of LIF-viral increases reparative remyelination
	DEVERMAN AND PATTERSON 2012 [52]
(iii)	Demyelination model: delivery of LIF-NP increases reparative remyelination.
	RITTCHEN ET AL [36]