Print Email Facebook Twitter Protective and therapeutic role for αB-crystallin in autoimmune demyelination Title Protective and therapeutic role for αB-crystallin in autoimmune demyelination Author Ousman, S.S. Tomooka, B.H. van Noort, J.M. Wawrousek, E.F. O'Conner, K. Hafler, D.A. Sobel, R.A. Robinson, W.H. Steinman, L. TNO Kwaliteit van Leven Publication year 2007 Abstract αB-crystallin (CRYAB) is the most abundant gene transcript present in early active multiple sclerosis lesions, whereas such transcripts are absent in normal brain tissue. This crystallin has anti-apoptotic and neuroprotective functions. CRYAB is the major target of CD4+ T-cell immunity to the myelin sheath from multiple sclerosis brain. The pathophysiological implications of this immune response were investigated here. We demonstrate that CRYAB is a potent negative regulator acting as a brake on several inflammatory pathways in both the immune system and central nervous system (CNS). Cryab-/- mice showed worse experimental autoimmune encephalomyelitis (EAE) at the acute and progressive phases, with higher Th1 and Th17 cytokine secretion from T cells and macrophages, and more intense CNS inflammation, compared with their wild-type counterparts. Furthermore, Cryab-/- astrocytes showed more cleaved caspase-3 and more TUNEL staining, indicating an anti-apoptotic function of Cryab. Antibody to CRYAB was detected in cerebrospinal fluid from multiple sclerosis patients and in sera from mice with EAE. Administration of recombinant CRYAB ameliorated EAE. Thus, the immune response against a negative regulator of inflammation, CRYAB, in multiple sclerosis, would exacerbate inflammation and demyelination. This can be countered by giving CRYAB itself for therapy of ongoing disease. ©2007 Nature Publishing Group. Subject Biomedical Researchcaspase 3cytokinegamma interferoninterleukin 12p40interleukin 17interleukin 2recombinant alphab crystallinrecombinant proteintumor necrosis factorantibodybraingeneimmune responseimmune systemnervous system disorderrodentallergic encephalomyelitisanimal cellanimal experimentanimal modelanimal tissueapoptosisarticleastrocytecentral nervous systemcerebrospinal fluidcontrolled studycytokine releasedemyelinationfemalegene functionhumanimmune responseimmune systemmacrophagemousemultiple sclerosismyelin sheathnick end labelingnonhumanpriority journalT lymphocyteTh1 cellwild typealpha-Crystallin B ChainAnimalsApoptosisAstrocytesCaspase 3Encephalomyelitis, Autoimmune, ExperimentalHumansInflammationMacrophagesMAP Kinase Signaling SystemMiceMultiple SclerosisMyelin SheathNeurogliaNeuroprotective AgentsNF-kappa BT-Lymphocytes, Helper-InducerMus To reference this document use: http://resolver.tudelft.nl/uuid:ef5dbbfd-93b9-4cbe-9f15-25e844b050b8 DOI https://doi.org/10.1038/nature05935 TNO identifier 240092 ISSN 0028-0836 Source Nature, 448 (7152), 474-479 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.