生物谷報道：蛋白質(zhì)B-crystallin主要存在于眼睛的晶狀體中，它在多發(fā)性硬化中所發(fā)生的炎癥和損傷的發(fā)展過程中可能是關(guān)鍵的“引爆點”,。過去,，人們知道它是多發(fā)性硬化患者體內(nèi)一個主要免疫目標(biāo)。現(xiàn)在,，用小鼠所做的研究工作表明,，該蛋白在一個多發(fā)性硬化模型中還扮演一個保護(hù)角色。當(dāng)將其注射進(jìn)實驗鼠體內(nèi)時,，它起一種消炎和神經(jīng)保護(hù)因子的作用,，并且還能使癱瘓發(fā)生逆轉(zhuǎn)。
原始出處:
Nature 448, 474-479 (26 July 2007) | doi:10.1038/nature05935; Received 6 March 2007; Accepted 17 May 2007; Published online 13 June 2007
Protective and therapeutic role for B-crystallin in autoimmune demyelination
Shalina S. Ousman1, Beren H. Tomooka2,3, Johannes M. van Noort4, Eric F. Wawrousek5, Kevin O'Conner6, David A. Hafler6, Raymond A. Sobel7, William H. Robinson2,3 & Lawrence Steinman1
Department of Neurology and Neurological Sciences, Stanford University
Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California 94305, USA
GRECC and,
Laboratory Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA
Department of Biosciences, TNO Quality of Life, 2301 CE Leiden, The Netherlands
National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Center for Neurologic Disease, Harvard Medical School, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
Correspondence to: Lawrence Steinman1 Correspondence and requests for materials should be addressed to L.S. (Email: [email protected]).
B-crystallin (CRYAB) is the most abundant gene transcript present in early active multiple sclerosis lesions, whereas such transcripts are absent in normal brain tissue1. This crystallin has anti-apoptotic2, 3, 4, 5, 6, 7 and neuroprotective8 functions. CRYAB is the major target of CD4+ T-cell immunity to the myelin sheath from multiple sclerosis brain9, 10. 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.
圖：Myelin antigen array analysis demonstrates antibody targeting of CRYAB in RRMS patients.
