Type I interferon receptor signalling is induced during demyelination while its function for myelin damage and repair is redundant.
The type I interferons, interferon-beta and alpha (IFN-beta, IFN-alpha), are widely used for the treatment of autoimmune demyelination in the central nervous system (CNS). Their effects on de- and remyelination through the broadly expressed type I IFN receptor (IFNAR), however, are highly speculative. In order to elucidate the role of endogenous type I interferons for myelin damage and recovery we induced toxic demyelination in the absence of IFNAR1. We demonstrate that IFNAR signalling was induced during acute demyelination since the cytokine IFN-beta as well as the IFN-dependent genes IRF7, ISG15 and UBP43 were strongly upregulated. Myelin damage, astrocytic and microglia response, however, were not significantly reduced in the absence of IFNAR1. Furthermore, motor skills of IFNAR1-deficient animals during non-immune demyelination were unaltered. Finally, myelin recovery was found to be independent from endogenous IFNAR signalling, indicating a redundant role of this receptor for non-inflammatory myelin damage and repair.
Schmidt
Hauke
H
Institute of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany.
Raasch
Jenni
J
Merkler
Doron
D
Klinker
Florian
F
Krauss
Sandra
S
Brück
Wolfgang
W
Prinz
Marco
M
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009048:Motor Skills / Q000502:physiology; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms
D005904:Glial Fibrillary Acidic Protein; D053633:Receptor, Interferon alpha-beta; D003471:Cuprizone