Citrullination of central nervous system proteins during the development of experimental autoimmune encephalomyelitis.
Immunization of mammals with central nervous system (CNS)-derived proteins or peptides induces experimental autoimmune encephalomyelitis (EAE), a disease resembling the human autoimmune disease multiple sclerosis (MS). Both diseases are accompanied by destruction of a part of the of the myelin sheaths, which surround neurites in the CNS. Previous studies in MS have described alterations in the citrullination of myelin basic protein, one of the main protein constituents of the myelin sheath. Here, we show that, also during the development of EAE in mice, hypercitrullination occurs in the areas of the spinal cord that show the highest degree of inflammation and that myelin basic protein and glial fibrillary acidic protein are among the hypercitrullinated proteins. We conclude that hypercitrullination of myelin proteins in the CNS is a common phenomenon in demyelinating disease. Hypercitrullination may cause conformational changes in proteins, so the affected proteins may be involved in the pathogenesis of CNS autoimmune disease by acting as autoreactive T-cell epitopes. This is the first report in which hypercitrullination of CNS proteins in EAE is described and in which proteins other than myelin basic protein are reported to be citrullinated during autoimmune-mediated CNS inflammation.
Raijmakers
Reinout
R
Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, NL-6500 HB Nijmegen, The Netherlands. R.Raijmakers@ncmls.ru.nl
Vogelzangs
Judith
J
Croxford
J Ludovic
JL
Wesseling
Pieter
P
van Venrooij
Walther J
WJ
Pruijn
Ger J M
GJ
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D002956:Citrulline / Q000276:immunology / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010446:Peptide Fragments; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C435023:myelin proteolipid protein (139-151); C018588:Luxol Fast Blue MBS; D002956:Citrulline; D006867:Hydrolases