Acute endotoxin-induced thymic atrophy is characterized by intrathymic inflammatory and wound healing responses.
Acute endotoxin-induced thymic atrophy is characterized by intrathymic inflammatory and wound healing responses.
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DOI：
10.1371/journal.pone.0017940
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发表时间：
2011-03-18
期刊：
影响因子：
3.7
通讯作者：
Sempowski GD
中科院分区：
文献类型：
--
作者：
Billard MJ;Gruver AL;Sempowski GD
高效的胸腺生成对于强大和健康的免疫系统至关重要。不幸的是，胸腺对压力非常敏感，导致退化和 T 细胞产量减少。胸腺复旧是许多临床情况的并发症，包括感染、营养不良、饥饿、放射或免疫抑制治疗。已知糖皮质激素和炎症细胞因子的全身升高会导致胸腺萎缩。然而，对于可能主动导致胸腺萎缩或在应激事件后启动胸腺恢复的胸腺内机制知之甚少。对内毒素血症诱导的胸腺复旧早期阶段的小鼠胸腺组织进行表型、组织学和转录组/通路分析，以确定应激期间驱动胸腺复旧的推定机制。该小鼠模型中胸腺萎缩通过参与 T 细胞发育、细胞活化和细胞周期进展的基因下调得到证实，与观察到的表型和组织学胸腺退化相关。显着的基因变化支持这样的假设：在应激诱导的胸腺复旧过程中，多个关键的胸腺内途径被差异激活。这些包括 LPS 通过 TLR 信号传导直接激活胸腺组织、炎性细胞因子的局部表达、T 细胞信号传导的抑制以及伤口愈合/组织重塑的诱导。总而言之，这些观察结果表明，除了经典的全身反应外，对内毒素攻击的直接胸腺内反应同时有助于内毒素血症期间的胸腺复旧。这些发现相对于目前对胸腺对应激反应的理解来说是一个重大进步，并可能导致开发新的治疗方法来改善与应激事件相关的免疫缺陷。
Productive thymopoiesis is essential for a robust and healthy immune system. Thymus unfortunately is acutely sensitive to stress resulting in involution and decreased T cell production. Thymic involution is a complication of many clinical settings, including infection, malnutrition, starvation, and irradiation or immunosuppressive therapies. Systemic rises in glucocorticoids and inflammatory cytokines are known to contribute to thymic atrophy. Little is known, however, about intrathymic mechanisms that may actively contribute to thymus atrophy or initiate thymic recovery following stress events. Phenotypic, histologic and transcriptome/pathway analysis of murine thymic tissue during the early stages of endotoxemia-induced thymic involution was performed to identify putative mechanisms that drive thymic involution during stress. Thymus atrophy in this murine model was confirmed by down-regulation of genes involved in T cell development, cell activation, and cell cycle progression, correlating with observed phenotypic and histologic thymus involution. Significant gene changes support the hypothesis that multiple key intrathymic pathways are differentially activated during stress-induced thymic involution. These included direct activation of thymus tissue by LPS through TLR signaling, local expression of inflammatory cytokines, inhibition of T cell signaling, and induction of wound healing/tissue remodeling. Taken together, these observations demonstrated that in addition to the classic systemic response, a direct intrathymic response to endotoxin challenge concurrently contributes to thymic involution during endotoxemia. These findings are a substantial advancement over current understanding of thymus response to stress and may lead to the development of novel therapeutic approaches to ameliorate immune deficiency associated with stress events.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
4
作者：
Gruver, Amanda L.;Ventevogel, Melissa S.;Sempowski, Gregory D.
通讯作者：
Sempowski, Gregory D.
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1073/pnas.94.17.9296
发表时间：
1997-08-19
影响因子：
11.1
作者：
Chambers, CA;Cado, D;Allison, JP
通讯作者：
Allison, JP