TY - JOUR
T1 - HLA-DRaα1-mMOG-35-55 treatment of experimental autoimmune encephalomyelitis reduces CNS inflammation, enhances M2 macrophage frequency, and promotes neuroprotection
AU - Benedek, Gil
AU - Meza-Romero, Roberto
AU - Jordan, Kelley
AU - Keenlyside, Lucy
AU - Offner, Halina
AU - Vandenbark, Arthur A.
N1 - Publisher Copyright:
© 2015 Benedek et al.
PY - 2015/6/24
Y1 - 2015/6/24
N2 - 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.
AB - 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.
KW - DRaα1-mMOG-35-55 therapy
KW - Experimental autoimmune encephalomyelitis (EAE)
KW - M2 macrophages
KW - Multiple sclerosis (MS)
KW - Neuroprotection
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U2 - 10.1186/s12974-015-0342-4
DO - 10.1186/s12974-015-0342-4
M3 - Article
C2 - 26104759
AN - SCOPUS:84933050077
SN - 1742-2094
VL - 12
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
IS - 1
M1 - 123
ER -