TY - JOUR
T1 - Apolipoprotein E mediation of neuro-inflammation in a murine model of multiple sclerosis
AU - Shin, Soomin
AU - Walz, Katharine A.
AU - Archambault, Angela S.
AU - Sim, Julia
AU - Bollman, Bryan P.
AU - Koenigsknecht-Talboo, Jessica
AU - Cross, Anne H.
AU - Holtzman, David M.
AU - Wu, Gregory F.
N1 - Funding Information:
We would like to thank Jungsu Kim, Jacob Basak, Laura Piccio and Robyn Klein for their helpful discussions and advice. We are indebted to N. Gretchen McGee for technical assistance with this research. Experimental support was provided by the Speed Congenics Facility of the Rheumatic Diseases Core Center at Washington University in St. Louis . As such, research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases , part of the National Institutes of Health , under Award Number P30AR048335 . This work was funded by the NINDS ( 5K08NS062138 ), the NIA ( AG13956 ), the McDonnell Center for Cellular and Molecular Neurobiology , and the Foundation for Barnes-Jewish Hospital . AHC was supported in part by the Manny & Rosalyn Rosenthal–Dr. John L. Trotter Chair in Neuroimmunology.
PY - 2014
Y1 - 2014
N2 - Apolipoprotein E (ApoE) functions as a ligand in receptor-mediated endocytosis of lipoprotein particles and has been demonstrated to play a role in antigen presentation. To explore the contribution of ApoE during autoimmune central nervous system (CNS) demyelination, we examined the clinical, cellular immune function, and pathologic consequences of experimental autoimmune encephalomyelitis (EAE) induction in ApoE knockout (ApoE-/-) mice. We observed reduced clinical severity of EAE in ApoE-/- mice in comparison to WT mice that was concomitant with an early reduction of dendritic cells (DCs) followed by a reduction of additional innate cells in the spinal cord at the peak of disease without any differences in axonal damage. While T cell priming was enhanced in ApoE-/- mice, reduced severity of EAE was also observed in ApoE-/- recipients of encephalitogenic wild type T cells. Expression of ApoE during EAE was elevated within the CNS of wild type mice, particularly by innate cells such as DCs. Overall, ApoE promotes clinical EAE, likely by mediation of inflammation localized within the CNS.
AB - Apolipoprotein E (ApoE) functions as a ligand in receptor-mediated endocytosis of lipoprotein particles and has been demonstrated to play a role in antigen presentation. To explore the contribution of ApoE during autoimmune central nervous system (CNS) demyelination, we examined the clinical, cellular immune function, and pathologic consequences of experimental autoimmune encephalomyelitis (EAE) induction in ApoE knockout (ApoE-/-) mice. We observed reduced clinical severity of EAE in ApoE-/- mice in comparison to WT mice that was concomitant with an early reduction of dendritic cells (DCs) followed by a reduction of additional innate cells in the spinal cord at the peak of disease without any differences in axonal damage. While T cell priming was enhanced in ApoE-/- mice, reduced severity of EAE was also observed in ApoE-/- recipients of encephalitogenic wild type T cells. Expression of ApoE during EAE was elevated within the CNS of wild type mice, particularly by innate cells such as DCs. Overall, ApoE promotes clinical EAE, likely by mediation of inflammation localized within the CNS.
KW - Antigen presentation
KW - Apolipoprotein E
KW - Dendritic cells
KW - EAE
UR - http://www.scopus.com/inward/record.url?scp=84900500473&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2014.03.010
DO - 10.1016/j.jneuroim.2014.03.010
M3 - Article
C2 - 24794230
AN - SCOPUS:84900500473
SN - 0165-5728
VL - 271
SP - 8
EP - 17
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -