Nature：蛋白质B-crystallin在多发性硬化中的作用

生物谷

生物谷报道：蛋白质B-crystallin主要存在于眼睛的晶状体中，它在多发性硬化中所发生的炎症和损伤的发展过程中可能是关键的“引爆点”。过去，人们知道它是多发性硬化患者体内一个主要免疫目标。现在，用小鼠所做的研究工作表明，该蛋白在一个多发性硬化模型中还扮演一个保护角色。当将其注射进实验鼠体内时，它起一种消炎和神经保护因子的作用，并且还能使瘫痪发生逆转。

原始出处:

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: steinman@stanford.edu).

alpha 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.