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IL10 deficiency promotes alveolar enlargement and lymphoid dysmorphogenesis in the aged murine lung.
Aging Cell ( IF 8.0 ) Pub Date : 2020-03-14 , DOI: 10.1111/acel.13130 Alla Malinina 1 , Dustin Dikeman 1 , Reyhan Westbrook 2 , Michelle Moats 1, 3 , Sarah Gidner 1 , Hataya Poonyagariyagorn 1 , Jeremy Walston 2 , Enid R Neptune 1
Aging Cell ( IF 8.0 ) Pub Date : 2020-03-14 , DOI: 10.1111/acel.13130 Alla Malinina 1 , Dustin Dikeman 1 , Reyhan Westbrook 2 , Michelle Moats 1, 3 , Sarah Gidner 1 , Hataya Poonyagariyagorn 1 , Jeremy Walston 2 , Enid R Neptune 1
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The connection between aging‐related immune dysfunction and the lung manifestations of aging is poorly understood. A detailed characterization of the aging IL10‐deficient murine lung, a model of accelerated aging and frailty, reconciles features of both immunosenescence and lung aging in a coherent model. Airspace enlargement developed in the middle‐aged (12 months old) and aged (20–22 months old) IL10‐deficient lung punctuated by an expansion of macrophages and alveolar cell apoptosis. Compared to wild‐type (WT) controls, the IL10‐deficient lungs from young (4‐month‐old) mice showed increased oxidative stress which was enhanced in both genotypes by aging. Active caspase 3 staining was increased in the alveolar epithelial cells of aged WT and mutant lungs but was greater in the IL10‐deficient milieu. Lung macrophages were increased in the aged IL10‐deficient lungs with exuberant expression of MMP12. IL10 treatment of naïve and M2‐polarized bone marrow‐derived WT macrophages reduced MMP12 expression. Conditioned media studies demonstrated the secretome of aged mutant macrophages harbors reduced AECII prosurvival factors, specifically keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF), promotes cell death, and reduces survival of primary alveolar epithelial cells. Compared to WT controls, aged IL10‐deficient mice have increased parenchymal lymphoid collections comprised of a reduced number of apoptotic cells and B cells. We establish that IL10 is a key modulator of airspace homeostasis and lymphoid morphogenesis in the aging lung enabling macrophage‐mediated alveolar epithelial cell survival and B‐cell survival within tertiary lymphoid structures.
中文翻译：
IL10缺乏促进老年鼠肺中肺泡增大和淋巴样畸变。
人们对与衰老相关的免疫功能障碍与肺部衰老表现之间的联系了解甚少。IL10缺陷型鼠肺衰老的详细特征，一种加速衰老和衰弱的模型，在一个连贯的模型中协调了免疫衰老和肺衰老的特征。在中年（12个月大）和年龄大（20-22个月大）的IL10缺陷型肺中，由于巨噬细胞的扩张和肺泡细胞凋亡而使空域扩大。与野生型（WT）对照相比，来自年轻（4个月大）小鼠的IL10缺陷型肺显示出增加的氧化应激，这两种基因型均随着衰老而增强。在衰老的WT和突变肺的肺泡上皮细胞中，活跃的caspase 3染色增加，但在IL10缺乏的环境中则增加。在IL10缺乏的老年肺中，巨噬细胞增多，MMP12表达旺盛。IL10治疗幼稚和M2极化的骨髓源性WT巨噬细胞可降低MMP12表达。有条件的媒体研究表明，老化的突变巨噬细胞的分泌组具有减少的AECII生存因子，特别是角质形成细胞生长因子（KGF）和肝细胞生长因子（HGF），可促进细胞死亡并减少原发性肺泡上皮细胞的存活。与野生型对照相比，IL10缺陷型老年小鼠的实质淋巴样收集物增多，凋亡细胞和B细胞数量减少。
更新日期：2020-03-14
中文翻译：
IL10缺乏促进老年鼠肺中肺泡增大和淋巴样畸变。
人们对与衰老相关的免疫功能障碍与肺部衰老表现之间的联系了解甚少。IL10缺陷型鼠肺衰老的详细特征，一种加速衰老和衰弱的模型，在一个连贯的模型中协调了免疫衰老和肺衰老的特征。在中年（12个月大）和年龄大（20-22个月大）的IL10缺陷型肺中，由于巨噬细胞的扩张和肺泡细胞凋亡而使空域扩大。与野生型（WT）对照相比，来自年轻（4个月大）小鼠的IL10缺陷型肺显示出增加的氧化应激，这两种基因型均随着衰老而增强。在衰老的WT和突变肺的肺泡上皮细胞中，活跃的caspase 3染色增加，但在IL10缺乏的环境中则增加。在IL10缺乏的老年肺中，巨噬细胞增多，MMP12表达旺盛。IL10治疗幼稚和M2极化的骨髓源性WT巨噬细胞可降低MMP12表达。有条件的媒体研究表明，老化的突变巨噬细胞的分泌组具有减少的AECII生存因子，特别是角质形成细胞生长因子（KGF）和肝细胞生长因子（HGF），可促进细胞死亡并减少原发性肺泡上皮细胞的存活。与野生型对照相比，IL10缺陷型老年小鼠的实质淋巴样收集物增多，凋亡细胞和B细胞数量减少。
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