Lack of B and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice
Lack of B and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice
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DOI：
10.1093/intimm/dxr017
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发表时间：
2011-05-01
影响因子：
4.4
通讯作者：
Nakajima, Hiroshi
中科院分区：
文献类型：
--
作者：
Oya, Yoshihiro;Watanabe, Norihiko;Nakajima, Hiroshi
MRL/Mp-Fas（lpr）（MRL-lpr）小鼠发生系统性自身免疫疾病，并且被认为是人类系统性红斑狼疮的良好模型。我们最近发现，缺乏B和T淋巴细胞衰减因子（BTLA）的小鼠，主要在淋巴细胞上表达的抑制性共受体，在129 SvEv背景下自发地在多个器官中发生淋巴细胞浸润和自身免疫性肝炎（AIH）样疾病。在这项研究中，我们研究了BTLA在MRL-lpr小鼠自身免疫性疾病发病机制中的作用。我们发现，与BTLA充足（BTLA（+/+））MRL lpr/lpr小鼠相比，BTLA（-/-）MRL lpr/lpr小鼠在唾液腺、肺、胰腺、肾和关节中发生严重的淋巴细胞浸润。此外，虽然在BTLA（+/+）MRL-lpr/lpr小鼠中未发现AIH样疾病，但与BTLA（-/-）129 SvEv小鼠相比，BTLA（-/-）MRL-lpr/lpr小鼠中的AIH样疾病加重。这些结果表明，BTLA在MRL-lpr小鼠的自身免疫性疾病中起保护作用，并且即使在不存在Fas依赖性信号传导的情况下，BTLA（-/-）小鼠也会发生AIH样疾病。
MRL/Mp-Fas (lpr) (MRL-lpr) mice develop a systemic autoimmune disease and are considered to be a good model for systemic lupus erythematosus in humans. We have recently shown that mice lacking B and T lymphocyte attenuator (BTLA), an inhibitory co-receptor expressed mainly on lymphocytes, on a 129SvEv background spontaneously develop lymphocytic infiltration in multiple organs and an autoimmune hepatitis (AIH)-like disease. In this study, we investigated the role of BTLA in the pathogenesis of autoimmune diseases in MRL-lpr mice. We found that BTLA-deficient (BTLA(-/-)) MRL-lpr/lpr mice developed severe lymphocytic infiltration in salivary glands, lungs, pancreas, kidneys and joints as compared with BTLA-sufficient (BTLA(+/+)) MRL-lpr/lpr mice. In addition, although AIH-like disease was not found in BTLA(+/+) MRL-lpr/lpr mice, AIH-like disease was exacerbated in BTLA(-/-) MRL-lpr/lpr mice as compared with that in BTLA(-/-) 129SvEv mice. These results suggest that BTLA plays a protective role in autoimmune diseases in MRL-lpr mice and that AIH-like disease develops in BTLA(-/-) mice even in the absence of Fas-dependent signaling.