Development of autoimmune hepatitis-like disease and production of autoantibodies to nuclear antigens in mice lacking B and T lymphocyte attenuator.
Development of autoimmune hepatitis-like disease and production of autoantibodies to nuclear antigens in mice lacking B and T lymphocyte attenuator.
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DOI：
10.1002/art.23674
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发表时间：
2008-08
影响因子：
--
通讯作者：
Saito, Yasushi
中科院分区：
文献类型：
--
作者：
Oya, Yoshihiro;Watanabe, Norihiko;Owada, Takayoshi;Oki, Mie;Hirose, Koichi;Suto, Akira;Kagami, Shin-ichiro;Nakajima, Hiroshi;Kishimoto, Takashi;Iwamoto, Itsuo;Murphy, Theresa L.;Murphy, Kenneth M.;Saito, Yasushi
B 和 T 淋巴细胞衰减因子 (BTLA) 是淋巴细胞上表达的辅助受体，最近被描述为负向调节淋巴细胞激活的抑制性辅助受体。本研究的目的是探讨BTLA在免疫稳态调节中的作用以及自身免疫的发病机制。我们检查了 BTLA 缺陷 (BTLA−/−) 小鼠的免疫球蛋白水平、核抗原自身抗体以及 T 细胞的激活状态。我们还检查了 BTLA−/− 小鼠器官的组织病理学变化。我们发现BTLA−/−小鼠逐渐出现高γ球蛋白血症、抗核抗体、抗SS-A抗体和抗双链DNA抗体，并且随着年龄的增长，外周活化的CD4+T细胞增多。缺乏 BTLA 会导致自身免疫性肝炎 (AIH) 样疾病自发发生，其特征是转氨酶升高、界面性肝炎和肝脏点状坏死。 BTLA−/− 小鼠的多个器官也显示出炎症细胞浸润，包括唾液腺、肺和胰腺，类似于干燥综合征（AIH 的常见并发症）。此外，BTLA−/− 小鼠在 7 个月后的存活率显着降低。我们的结果表明，BTLA 在维持免疫耐受和预防自身免疫性疾病方面发挥着重要作用。
B and T lymphocyte attenuator (BTLA), a coreceptor expressed on lymphocytes, has recently been described as an inhibitory coreceptor that negatively regulates lymphocyte activation. The purpose of this study was to investigate the role of BTLA in the regulation of immune homeostasis and the pathogenesis of autoimmunity. We examined the levels of immunoglobulins, autoantibodies to nuclear antigens, and activation status of T cells in BTLA-deficient (BTLA−/−) mice. We also examined histopathologic changes of the organs in BTLA−/− mice. We found that BTLA−/− mice gradually developed hyper-γ-globulinemia, antinuclear antibody, anti-SS-A antibody and anti-double-strand DNA antibody, and an increase of activated CD4+ T cells in the periphery with age. Lack of BTLA led to spontaneous development of autoimmune hepatitis (AIH)-like disease characterized by elevation of transaminases and interface hepatitis and spotty necrosis in the liver. BTLA−/− mice also showed inflammatory cell infiltration in multiple organs including salivary glands, lungs and pancreas, similar to Sjögren’s syndrome, a frequent complication of AIH. Furthermore, BTLA−/− mice showed a significant reduction in the survival rate after the age of 7 months. Our results indicate that BTLA plays an important role in the maintenance of immune tolerance and the prevention of autoimmune diseases.
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影响因子：
15.3
作者：
Kaneko, Y;Harada, M;Kawano, T;Yamashita, M;Shibata, Y;Gejyo, F;Nakayama, T;Taniguchi, M
通讯作者：
Taniguchi, M
影响因子：
--
作者：
Matsumoto, K;Watanabe, N;Saito, T
通讯作者：
Saito, T
影响因子：
25.7
作者：
LINDGREN, S;MANTHORPE, R;ERIKSSON, S
通讯作者：
ERIKSSON, S
影响因子：
64.8
作者：
MACDONALD, HR;SCHNEIDER, R;HENGARTNER, H
通讯作者：
HENGARTNER, H
影响因子：
82.9
作者：
Okazaki, T;Tanaka, Y;Honjo, T
通讯作者：
Honjo, T