HLA-DRaα1-mMOG-35-55 treatment of experimental autoimmune encephalomyelitis reduces CNS inflammation,enhances M2 macrophage frequency,and promotes neuroprotection

Background: draα1-mouse(m)mog-35-55,a novel construct developed in our laboratory as a simpler and potentially less immunogenic alternative to two-domain class ii constructs,was shown previously to target the mif/cd74 pathway and to reverse clinical and histological signs of experimental autoimmune encephalomyelitis (eae) in dr*1501-tg mice in a manner similar to the parent dr2β1-containing construct. methods: in order to determine whether draα1-mmog-35-55 could treat eae in major histocompatibility complex (mhc)-mismatched mice and to evaluate the treatment effect on central nervous system (cns) inflammation,c57bl/6 mice were treated with draα1-mmog-35-55. in addition,gene expression profile was analyzed in spinal cords of eae dr*1501-tg mice that were treated with draα1-mmog-35-55. results: we here demonstrate that draα1-mmog-35-55 could effectively treat eae in mhc-mismatched c57bl/6 mice by reducing cns inflammation,potentially mediated in part through an increased frequency of m2 monocytes in the spinal cord. microarray analysis of spinal cord tissue from draα1-mmog-35-55-treated vs. vehicle control mice with eae revealed decreased expression of a large number of pro-inflammatory genes including cd74,nlrp3,and il-1β and increased expression of genes involved in myelin repair (mbp) and neuroregeneration (huwe1). conclusion: these findings indicate that the draα1-mmog-35-55 construct retains therapeutic,anti-inflammatory,and neuroprotective activities during treatment of eae across mhc disparate barriers. © 2015 benedek et al.