Table 1. Most significantly upregulated genes (>16 fold change) with non-immunological functions.

Entrez Gene	Entrez Name	log2 fold change	p value	Gene ontology processes associated with EAE	Association with chronic EAE processes, differentiation, de/remyelination, neurodegeneration, neuroprotection
Mbp	myelin basic protein	inf	N/A	Myelination	Myelin constituent. Highly upregulated during oligodendrocyte differentiation [22].
Plp1	proteolipid protein (myelin) 1	inf	N/A	Myelination	Myelin constituent. Highly upregulated during oligodendrocyte differentiation [22].
Mmp12	matrix metallopeptidase 12	inf	5.00E-05	Positive regulation of epithelial cell proliferation involved in wound healing	Extracellular protease expressed in active macrophages in MS lesions [23]. Involved in the pathogenesis of Theiler’s murine encephalopathy, induces demyelination and neurotoxicity [24].
Mcoln3	mucolipin 3	inf	5.00E-05	Auditory receptor cell differentiation, ion transport	Transient receptor potential channel (TRPML3) involved in endocytosis [25], localized to lysosomes and initiates neutralised lysosome exocytosis [26].
Atp6v0d2	ATPase, H+ transporting, lysosomal V0 subunit D2	inf	5.00E-05	ATP hydrolysis coupled proton transport	Regulator of bone formation [27], no identified role.
Gpnmb	glycoprotein (transmembrane) nmb	7.09385	5.00E-05	Cell adhesion	Upregulated in Lewis rat EAE [28] and in an amyotrophic lateral sclerosis mouse model, proposed neuroprotective role [29].
Wisp2	WNT1 inducible signaling pathway protein 2	6.21785	5.00E-05	Cell adhesion, cell growth regulation	Promotes neurite outgrowth in ganglioside deficient mice [30].
Plin4	perilipin 4	5.82633	5.00E-05	Lipid storage regulation	Protein present in spinal cord, involved in lipid droplet storage [31]
Steap4	STEAP family member 4	5.37493	5.00E-05	Ion transport	Involved in osteoclast differentiation [32], no identified role.
Ms4a7	membrane-spanning 4-domains, subfamily A, member 7	5.34068	0.0001	Unknown	No identified role. Associated with late-onset Alzheimer’s disease [33]
Gm4841	predicted gene 4841	5.20993	0.0007	Unknown	No identified role.
Cybb	cytochrome b-245, beta polypeptide	5.02298	5.00E-05	Immune response, ion transport	Superoxide generating enzyme Nox2, implicated in microglial induced neurodegeneration [34]
Gpr65	G-protein coupled receptor 65	4.94688	0.0026	G-protein coupled receptor signaling pathway	Proton sensing TDAG8 receptor, involved in osteoclast regulation [35].
Ch25h	cholesterol 25-hydroxylase	4.91766	5.00E-05	Cholesterol metabolism	Proposed susceptibility gene for Alzheimer’s disease [36]. Proinflammatory enzyme, ch25h deletion attenuates EAE [37].
Sprr1a	small proline-rich protein 1A	4.60697	0.0026	Keratinocyte differentiation	Protein expressed after neuronal injury, involved in neuronal regeneration processes [38–40].
Ppl	periplakin	4.55594	0.0026	Unknown	Abundant in the brain, opioid receptor interacting protein [41], no identified role.
Xdh	xanthine dehydrogenase	4.4114	5.00E-05	Cell differentiation/apoptosis	Xanthine oxidase, the metabolic product of xanthine dehydrogenase, is Implicated in EAE pathogenesis, axonal and myelin loss [42].
Wfdc17	WAP four-disulfide core domain 17	4.38813	5.00E-05	Unknown	Anti-neuroinflammatory microglial protein [43].
Osm	oncostatin M	4.30594	0.0026	Immune response, peripheral nervous system development	Upregulated in relapsing-remitting MS patients [44], protective against demyelination in the Cuprizone-induced demyelination model [45].
Ms4a6d	membrane-spanning 4-domains, subfamily A, member 6D	4.26213	5.00E-05	Unknown	No identified role.
Rnf186	ring finger protein 186	4.0977	0.0007	Unknown	No identified role.
Gpr114	adhesion G protein-coupled receptor G5	4.09084	0.00345	G-protein coupled receptor signaling pathway	No identified role.
Tnfsf11	tumor necrosis factor (ligand) superfamily, member 11	4.07763	0.00275	Immune response, cell differentiation	Osteoprotegerin ligand RANKL, important osteoclast differentiation factor [46]. Upregulated in MS patients [47, 48].
Serpina3i	serine (or cysteine) peptidase inhibitor, clade A, member 3I	4.05241	5.00E-05	Unknown	No identified role.
B430306N03Rik	RIKEN cDNA B430306N03 gene	4.04922	5.00E-05	Unknown	Unknown protein.