Deletion of FoxN1 in the thymic medullary epithelium reduces peripheral T cell responses to infection and mimics changes of aging.
Deletion of FoxN1 in the thymic medullary epithelium reduces peripheral T cell responses to infection and mimics changes of aging.
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DOI：
10.1371/journal.pone.0034681
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Shams H
中科院分区：
文献类型：
--
作者：
Guo J;Feng Y;Barnes P;Huang FF;Idell S;Su DM;Shams H
衰老增加了对感染的易感性，部分原因是胸腺退化最终导致naïve t淋巴细胞输出减少。胸腺上皮细胞（TECs）对确保胸腺细胞的正常成熟和外周血T细胞的产生至关重要。叉头类转录因子由FoxN1编码，在产前和产后胸腺中调控TECs的发育、分化和功能。我们最近发现，表达角蛋白14 （K14）的上皮细胞表达FoxN1对于维持胸腺髓质结构至关重要，而在K14启动子驱动的tec中，FoxN1的缺失抑制了成熟tec的发育并减少了胸腺细胞总数。这些发现让人想起在正常胸腺衰老过程中观察到的变化。在当前的报告中，我们在小鼠模型中比较了k14驱动的FoxN1缺失对响应流感病毒感染的外周T细胞功能的影响与正常衰老相关的影响。foxn1缺失小鼠外周血CD62L+CD44−naïve t细胞数量减少。此外，在流感感染期间，这些动物对流感病毒的抗原特异性CD8+ t细胞和IgG反应降低，并伴有肺损伤、体重减轻和死亡率增加。这些发现与在老年野生型小鼠中观察到的结果相似，提供了第一个证据，证明k14介导的FoxN1缺失导致t细胞功能的变化，类似于在感染因子攻击的免疫反应中衰老的变化。
Aging increases susceptibility to infection, in part because thymic involution culminates in reduced naïve T-lymphocyte output. Thymic epithelial cells (TECs) are critical to ensure normal maturation of thymocytes and production of peripheral T cells. The forkhead-class transcription factor, encoded by FoxN1, regulates development, differentiation, and function of TECs, both in the prenatal and postnatal thymus. We recently showed that expression of FoxN1, by keratin 14 (K14)-expressing epithelial cells is essential for maintenance of thymic medullary architecture, and deletion of FoxN1 in K14 promoter-driven TECs inhibited development of mature TECs and reduced the number of total thymocytes. These findings are reminiscent of changes observed during normal thymic aging. In the current report, we compared the effects of K14-driven FoxN1 deletion on peripheral T cell function in response to influenza virus infection with those associated with normal aging in a mouse model. FoxN1-deleted mice had reduced numbers of peripheral CD62L+CD44− naïve T-cells. In addition, during influenza infection, these animals had reduced antigen-specific CD8+ T-cell and IgG responses to influenza virus, combined with increased lung injury, weight loss and mortality. These findings paralleled those observed in aged wild type mice, providing the first evidence that K14-mediated FoxN1 deletion causes changes in T-cell function that mimic those in aging during an immune response to challenge with an infectious agent.
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影响因子：
56.9
作者：
Nehls, M;Kyewski, B;Boehm, T
通讯作者：
Boehm, T
DOI：
10.1016/j.amjopharm.2010.05.003
发表时间：
2010-06-01
期刊：
AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY
影响因子：
--
作者：
Stuart, Bruce;Davidoff, Amy;Kemner, Jason
通讯作者：
Kemner, Jason
DOI：
10.4049/jimmunol.182.2.784
发表时间：
2009-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ahmed M;Lanzer KG;Yager EJ;Adams PS;Johnson LL;Blackman MA
通讯作者：
Blackman MA
影响因子：
7.8
作者：
Zhu, Xike;Gui, Jingang;Su, Dong-Ming
通讯作者：
Su, Dong-Ming
影响因子：
5.5
作者：
Zhou, Xin;McElhaney, Janet E.
通讯作者：
McElhaney, Janet E.