Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced type 1 diabetes.
Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced type 1 diabetes.
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DOI：
10.1038/gene.2013.31
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发表时间：
2013-09
影响因子：
5
通讯作者：
Hessner, M. J.
中科院分区：
文献类型：
--
作者：
Chen, Y-G;Mordes, J. P.;Blankenhorn, E. P.;Kashmiri, H.;Kaldunski, M. L.;Jia, S.;Geoffrey, R.;Wang, X.;Hessner, M. J.
与1型糖尿病（T1 D）相关的稀释血浆细胞因子环境虽然难以直接测量，但足以在使用健康白细胞作为报告基因的生物测定中驱动转录。以前，我们报告了T1 D患者和BioBreeding（BB）大鼠模型中与疾病相关的部分IL-1依赖性转录特征。在这里，我们检查时间签名在同类BBDR。lyp/lyp大鼠自发T1 D，和BBDR大鼠T1 D的进展后，只有在年轻的动物免疫扰动。断奶后，BBDR时间特征显示与先天性炎症相关的转录以及IL-10和TGF-β介导的调节的早期同步诱导。BBDR血浆细胞因子水平反映了显示早期炎症的特征，随后诱导了与病毒未能诱导老年大鼠T1 D相关的调节状态。相比之下，BBDR.lyp/lyp时间特征表现出异步动力学，延迟诱导炎性转录，随后诱导较弱的调节性转录，这与它们在调节性T细胞中的缺陷一致。通过对BB大鼠和人类T1 D进展者的血浆诱导特征的纵向分析，我们已经确定了减弱BBDR大鼠中预先存在的先天性炎症状态的免疫调节过程的变化，这表明T1 D易感性随年龄下降的机制。
The dilute plasma cytokine milieu associated with Type 1 diabetes (T1D), while difficult to measure directly, is sufficient to drive transcription in a bioassay that uses healthy leukocytes as reporters. Previously, we reported disease-associated, partially IL-1 dependent, transcriptional signatures in both T1D patients and the BioBreeding (BB) rat model. Here we examine temporal signatures in congenic BBDR.lyp/lyp rats that develop spontaneous T1D, and BBDR rats where T1D progresses only after immunological perturbation in young animals. After weaning, the BBDR temporal signature showed early coincident induction of transcription related to innate inflammation as well as IL-10- and TGF-β-mediated regulation. BBDR plasma cytokine levels mirrored the signatures showing early inflammation, followed by induction of a regulated state that correlated with failure of virus to induce T1D in older rats. In contrast, the BBDR.lyp/lyp temporal signature exhibited asynchronous dynamics, with delayed induction of inflammatory transcription and later, weaker induction of regulatory transcription, consistent with their deficiency in regulatory T cells. Through longitudinal analyses of plasma induced signatures in BB rats and a human T1D progressor, we have identified changes in immunoregulatory processes that attenuate a preexisting innate inflammatory state in BBDR rats, suggesting a mechanism underlying the decline in T1D susceptibility with age.
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影响因子：
3.7
作者：
Akimova T;Beier UH;Wang L;Levine MH;Hancock WW
通讯作者：
Hancock WW
影响因子：
20.3
作者：
Gaultier, Alban;Arandjelovic, Sanja;Gonias, Steven L.
通讯作者：
Gonias, Steven L.
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
影响因子：
4.6
作者：
English, K.;Ryan, J. M.;Mahon, B. P.
通讯作者：
Mahon, B. P.
影响因子：
4.4
作者：
Gottschalk, Rachel A.;Corse, Emily;Allison, James P.
通讯作者：
Allison, James P.