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Low expression of complement inhibitory protein CD59 contributes to humoral autoimmunity against astrocytes.
Wang, Zhen; Guo, Wen; Liu, Yuanchu; Gong, Ye; Ding, Xiaoli; Shi, Kaibin; Thome, Rodolfo; Zhang, Guang-Xian; Shi, Fu-Dong; Yan, Yaping.
Afiliação
  • Wang Z; Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • Guo W; Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • Liu Y; Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710000, China.
  • Gong Y; Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710000, China.
  • Ding X; Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710000, China.
  • Shi K; Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • Thome R; Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
  • Zhang GX; Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
  • Shi FD; Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
  • Yan Y; Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangere
Brain Behav Immun ; 65: 173-182, 2017 Oct.
Article em En | MEDLINE | ID: mdl-28476558
Neuromyelitis optica spectrum disorder is primarily an anti-aquaporin 4 autoantibody-mediated, central nervous system-restricted channelopathy. Patients frequently develop central nervous system-restricted lesions even though autoantigen aquaporin 4 in neuromyelitis optica spectrum disorder is broadly distributed in the central nervous system and peripheral organs. The cause of such tissue-specific immune response remains largely unknown. We confirmed here that CD59, an inhibitory regulator of the complement membrane attack complex, is expressed and co-localized with aquaporin 4 in peripheral organs but is only minimally expressed in astrocytes in the central nervous system. In addition, we further found that CD59 overexpression in mouse brains decreased demyelination, blocked the loss of astrocytes and aquaporin 4, and inhibited membrane attack complex formation and infiltration of inflammatory cells. Inactivation of CD59 in mouse peripheral aquaporin 4-expressing cells and tissues led to complement-dependent cytotoxicity. In accordance with the mouse data, human samples presented higher expression of CD59 in many aquaporin 4-expressing peripheral tissues but not in astrocytes. Silencing or blocking CD59 in aquaporin 4-expressing human tracheal epithelial and skeletal muscle cells induced membrane attack complex formation and cytotoxicity, which suggests a protective role of CD59 in anti-aquaporin 4 antibodies-mediated complement toxicity. Our findings suggest that low CD59 expression in astrocytes may contribute to central nervous system-restricted lesions in neuromyelitis optica spectrum disorder. Restoring CD59 expression in astrocytes may serve as a novel therapeutic target of neuromyelitis optica spectrum disorder.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Astrócitos / Antígenos CD59 Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Astrócitos / Antígenos CD59 Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article