Severe tissue trauma triggers the autoimmune state systemic lupus erythematosus in the MRL/++ lupus-prone mouse
Severe tissue trauma triggers the autoimmune state systemic lupus erythematosus in the MRL/++ lupus-prone mouse
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DOI：
10.1177/0961203308097479
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发表时间：
2009-04-01
期刊：
影响因子：
2.6
通讯作者：
Davis, T. A.
中科院分区：
文献类型：
--
作者：
Anam, K.;Amare, M.;Davis, T. A.
与严重损伤相关的组织损伤可导致严重的炎症反应，可能引发狼疮易感个体的自身免疫发展。在这项研究中，我们研究了大面积全层皮肤烧伤在狼疮易发MRL/++小鼠自身免疫性疾病早期发病中的作用。MRL/++小鼠（慢性模型）在bb0 ~ 70周龄时表现出自身免疫症状，而MRL/-Fas（lpr）小鼠（急性模型）由于淋巴细胞增生性突变在1722周龄时出现自身免疫疾病。mrl /++小鼠（损伤后4-15周）发生的自身免疫性疾病表现为皮肤病变、血管炎、表皮溃疡、细胞浸润、脾肿大、淋巴结病、高γ球蛋白血症、自身抗体升高和肾脏病变，包括蛋白尿、肾小球肾炎和免疫复合物沉积；导致生存率降低的并发症。对伤口边缘组织的转录研究表明，在伤口早期愈合过程中，IL-1 β、IL-6、tnf - α和PGE(2)合成失调的致病作用与自身免疫性疾病的早期发病之间存在相关性。有趣的是，伤口愈合的MRL/++小鼠（烧伤后30-40天）强烈排斥皮肤同种移植物。相反，移植到年龄匹配的MRL/++幼崽身上的皮肤等移植物获得了长期存活。总之，这些发现表明，创伤性损伤加剧了狼疮易感小鼠的炎症性皮肤病和严重的多器官发病机制。狼疮（2009）18,318-331。
Tissue damage associated with a severe injury can result in profound inflammatory responses that may trigger autoimmune development in lupus-prone individuals. In this study, we investigated the role of a large full-thickness cutaneous burn injury on the early onset of autoimmune disease in lupus-prone MRL/++ mice. MRL/++ mice (chronic model) exhibit autoimmune symptoms at > 70 weeks of age, whereas MRL/-Fas(lpr) mice (acute model) develop autoimmune disease in 17 22 weeks due to a lymphoproliferative mutation. Autoimmune disease developed inMRL/++ mice (4-15 weeks post injury) is manifested by skin lesions, vasculitis, epidermal ulcers, cellular infiltration, splenomegaly, lymphadenopathy, hypergammaglobulinemia, elevated autoantibodies and renal pathologies including proteinuria, glomerulonephritis and immune complex deposition; complications that contribute to reduced survival. Transcription studies of wound margin tissue show a correlation between the pathogenic effects of dysregulated IL-1 beta, IL-6, TNF-alpha and PGE(2) synthesis during early wound healing and early onset of autoimmune disease. Interestingly, MRL/++ mice with healed wounds (30-40 days post burn) strongly rejected skin isografts. Conversely, skin isografts transplanted onto naive age-matched MRL/++ littermates achieved long-term survival. Collectively, these findings suggest that traumatic injury exacerbates inflammatory skin disease and severe multi-organ pathogenesis in lupus-prone mice. Lupus (2009) 18, 318-331.