A novel model of rheumatoid arthritis-associated interstitial lung disease in SKG mice
A novel model of rheumatoid arthritis-associated interstitial lung disease in SKG mice
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DOI：
10.3109/01902148.2011.636139
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发表时间：
2012-03-01
影响因子：
1.7
通讯作者：
Riches, David W. H.
中科院分区：
文献类型：
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作者：
Keith, Rebecca C.;Powers, Jennifer L.;Riches, David W. H.
类风湿关节炎相关间质性肺疾病 (RA-ILD) 与高达 10% 的类风湿关节炎患者死亡率增加相关。肺部暴露于香烟烟雾与疾病的发展有关。人们对 RA-ILD 发展的机制知之甚少，部分原因是缺乏合适的小鼠模型。本研究的目的是（i）测试 SKG 小鼠作为自身免疫性关节炎中细胞性和纤维化间质性肺炎模型的适用性，以及（ii）确定肺损伤在 SKG 小鼠关节炎发展中的作用。通过流式细胞术和组织学定量支气管肺泡灌洗中的细胞积累、静态顺应性、胶原水平和浸润细胞表型来评估关节炎 SKG 小鼠的肺组织。肺损伤是由接触香烟烟雾或博来霉素引起的。患有关节炎的 SKG 小鼠出现了斑片状细胞和纤维化间质性肺炎，与静态顺应性降低、胶原蛋白水平增加和炎症细胞积聚相关。浸润细胞包括CD4(+)T细胞、B细胞、巨噬细胞和中性粒细胞。长期接触香烟烟雾或博莱霉素引起的肺损伤不会引起关节炎。肺部疾病的模式表明，关节炎 SKG 小鼠代表了 RA-ILD 患者非特异性间质性肺炎的真实模型。吸烟或肺损伤后关节炎没有发生，这表明仅由肺部炎症和损伤引起免疫耐受破坏的模型可能过于简单化。
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is associated with increased mortality in up to 10% of patients with rheumatoid arthritis. Lung exposure to cigarette smoke has been implicated in disease development. Little is known about the mechanisms underlying the development of RA-ILD, in part due to the lack of an appropriate mouse model. The objectives of this study were (i) to test the suitability of SKG mice as a model of cellular and fibrotic interstitial pneumonia in the setting of autoimmune arthritis, and (ii) to determine the role of lung injury in the development of arthritis in SKG mice. Lung tissues were evaluated in arthritic SKG mice by quantifying cell accumulation in bronchoalveolar lavage, static compliance, collagen levels, and infiltrating cell phenotypes by flow cytometry and histology. Lung injury was induced by exposure to cigarette smoke or bleomycin. Arthritic SKG mice developed a patchy cellular and fibrotic interstitial pneumonia associated with reduced static compliance, increased collagen levels, and accumulation of inflammatory cells. Infiltrating cells comprised CD4(+) T cells, B cells, macrophages, and neutrophils. Chronic exposure to cigarette smoke or initiation of lung injury with bleomycin did not cause arthritis. The pattern of lung disease suggests that arthritic SKG mice represent an authentic model of nonspecific interstitial pneumonia in RA-ILD patients. The lack of arthritis development after cigarette smoke or lung injury suggests that a model where breaches in immunologic tolerance are induced by lung inflammation and injury alone may be overly simplistic.