The prolyl isomerase Pin1 modulates development of CD8+ cDC in mice.
The prolyl isomerase Pin1 modulates development of CD8+ cDC in mice.
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DOI：
10.1371/journal.pone.0029808
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Means AR
中科院分区：
文献类型：
--
作者：
Barberi TJ;Dunkle A;He YW;Racioppi L;Means AR
Pin1 先前已被描述为调节参与先天免疫和适应性免疫的细胞。然而，到目前为止，Pin1 在调节传统树突状细胞（可有效激活幼稚 T 细胞）从而桥接先天性和适应性免疫反应的先天性抗原呈递细胞方面的作用尚未被描述。当用 LPS 攻击时，Pin1 缺失小鼠无法在脾脏中积累常规树突状细胞 (cDC)。对稳态脾 DC 群体的分析表明，Pin1 缺失小鼠的 CD8+ cDC 较少。通过用 DC 指导性细胞因子 Flt3 配体培养 Pin1-null 骨髓，重现了这种缺陷。此外，注射 Flt3 配体 9 天未能诱导 Pin1 缺失小鼠中 CD8+ cDC 的强劲扩增。感染单核细胞增多性李斯特菌后，Pin1 缺失小鼠在刺激过继转移的 WT CD8+ T 细胞增殖方面存在缺陷，这表明 Pin1 缺失 CD8+ cDC 的减少可能会影响体内 T 细胞对感染的反应。最后，在分析 DC 发育中涉及的蛋白质表达后，在 Pin1 缺失细胞中检测到 PU.1 表达升高，这是由于 PU.1 蛋白质半衰期延长所致。我们已经确定了 Pin1 作为 CD8+ cDC 发育调节器的新作用。与 Pin1 缺失小鼠中 CD8+ cDC 数量减少一致，我们发现 Pin1 的缺失会损害单核细胞增生李斯特氏菌感染时的 CD8+ T 细胞增殖。这些数据表明，通过调节 CD8+ cDC 的产生，Pin1 可能作为适应性免疫的重要调节剂。
Pin1 has previously been described to regulate cells that participate in both innate and adaptive immunity. Thus far, however, no role for Pin1 has been described in modulating conventional dendritic cells, innate antigen presenting cells that potently activate naïve T cells, thereby bridging innate and adaptive immune responses. When challenged with LPS, Pin1-null mice failed to accumulate spleen conventional dendritic cells (cDC). Analysis of steady-state spleen DC populations revealed that Pin1-null mice had fewer CD8+ cDC. This defect was recapitulated by culturing Pin1-null bone marrow with the DC-instructive cytokine Flt3 Ligand. Additionally, injection of Flt3 Ligand for 9 days failed to induce robust expansion of CD8+ cDC in Pin1-null mice. Upon infection with Listeria monocytogenes, Pin1-null mice were defective in stimulating proliferation of adoptively transferred WT CD8+ T cells, suggesting that decreases in Pin1 null CD8+ cDC may affect T cell responses to infection in vivo. Finally, upon analyzing expression of proteins involved in DC development, elevated expression of PU.1 was detected in Pin1-null cells, which resulted from an increase in PU.1 protein half-life. We have identified a novel role for Pin1 as a modulator of CD8+ cDC development. Consistent with reduced numbers of CD8+ cDC in Pin1-null mice, we find that the absence of Pin1 impairs CD8+ T cell proliferation in response to infection with Listeria monocytogenes. These data suggest that, via regulation of CD8+ cDC production, Pin1 may serve as an important modulator of adaptive immunity.
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影响因子：
3.2
作者：
Hock, H;Orkin, SH
通讯作者：
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影响因子：
3.7
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Simon, M. Celeste
影响因子：
4.4
作者：
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通讯作者：
Heath, WR