Loss of LFA-1, but not Mac-1, protects MRL/MpJ-Fas1pr mice from autoimmune disease
Loss of LFA-1, but not Mac-1, protects MRL/MpJ-Fas1pr mice from autoimmune disease
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DOI：
10.1016/s0002-9440(10)63325-1
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发表时间：
2004-08-01
影响因子：
6
通讯作者：
Bullard, DC
中科院分区：
文献类型：
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作者：
Kevil, CG;Hicks, MJ;Bullard, DC
系统性红斑狼疮（SLE）是一种以免疫复合物介导的组织损伤为特征的自身免疫性疾病。许多不同的粘附分子被认为参与SLE的发展，然而，很少有研究直接检查这些蛋白质的贡献。在这里，我们证明了LXA-1在MRL/MpJ-Fas（1 pr）小鼠狼疮的发展中起着至关重要的作用。缺乏LFA-1但不缺乏Mac-1的小鼠表现出存活率显著增加，抗DNA自身抗体形成减少，肾小球肾炎减少。LFA-1缺陷小鼠的表型与β 2整合素缺陷（CD 18-null）MRL/MpJ-Fas（1 pr）小鼠中观察到的表型相似，表明β 2整合素家族成员和其他粘附分子之间缺乏冗余。这些研究确定LFA-1是该模型中自身免疫性疾病发病机制的关键因素，并进一步表明靶向这种粘附分子的治疗策略可能有利于SLE的治疗。
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex-mediated tissue injury. Many different adhesion molecules are thought to participate in the development of SLE; however, few studies have directly examined the contributions of these proteins. Here we demonstrate that LXA-1 plays an essential role in the development of lupus in MRL/MpJ-Fas(1pr) mice. Mice deficient in LFA-1, but not Mac-1, showed significantly increased survival, decreased anti-DNA autoantibody formation, and reduced glomerulonephritis. The phenotype of the LFA-1-deficient mice was similar to that observed in beta(2) integrin-deficient (CD18-null) MRL/MpJ-Fas(1pr) mice, suggesting a lack of redundancy among the beta(2) integrin family members and other adhesion molecules. These studies identify LFA-1 as a key contributor in the pathogenesis of autoimmune disease in this model, and further suggest that therapeutic strategies targeting this adhesion molecule may be beneficial for the treatment of SLE.