Retinoic acid treated human dendritic cells induce T regulatory cells via the expression of CD141 and GARP which is impaired with age.
Retinoic acid treated human dendritic cells induce T regulatory cells via the expression of CD141 and GARP which is impaired with age.
复制标题
维甲酸处理的人树突状细胞通过CD141和GARP的表达诱导T调节细胞，而GARP随着年龄的增长而受损。
DOI：
10.18632/aging.100973
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Agrawal A
中科院分区：
文献类型：
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作者：
Agrawal S;Ganguly S;Tran A;Sundaram P;Agrawal A
老年受试者对粘膜疾病的易感性增加。视黄酸（Retinoic Acid， RA）在粘膜耐受诱导中起重要作用。RA作用于树突状细胞（dc）诱导粘膜耐受。在这里，我们比较了老年人和年轻人的dc对RA的反应，以了解dc在年龄相关的粘膜疾病易感性增加中的作用。我们的研究显示，与年轻dc相比，RA刺激的老年dc在诱导IL-10和T调节细胞方面存在缺陷。对潜在机制的检查表明，RA暴露导致dc上CD141和GARP的上调，从而使dc产生耐受性。与CD141lo和GARP−dc相比，CD141hi、GARP+ dc诱导T调节性细胞的能力增强。与RA刺激的年轻dc不同，老年dc表现出CD141和GARP上调的减弱。在RA治疗中，老年dc中表达CD141和GARP的百分比显著降低。此外，来自老年人的剩余CD141hi， GARP+ dc也缺乏诱导T regs。综上所述，老年dc对RA反应的降低增强了老年人的黏膜炎症，增加了他们对粘膜疾病的易感性。
Aged subjects display increased susceptibility to mucosal diseases. Retinoic Acid (RA) plays a major role in inducing tolerance in the mucosa. RA acts on Dendritic cells (DCs) to induce mucosal tolerance. Here we compared the response of DCs from aged and young individuals to RA with a view to understand the role of DCs in age-associated increased susceptibility to mucosal diseases. Our investigations revealed that compared to young DCs, RA stimulated DCs from aged subjects are defective in inducing IL-10 and T regulatory cells. Examinations of the underlying mechanisms indicated that RA exposure led to the upregulation of CD141 and GARP on DCs which rendered the DCs tolerogenic. CD141hi, GARP+ DCs displayed enhanced capacity to induce T regulatory cells compared to CD141lo and GARP− DCs. Unlike RA stimulated DCs from young, DCs from aged subjects exhibited diminished upregulation of both CD141 and GARP. The percentage of DCs expressing CD141 and GARP on RA treatment was significantly reduced in DCs from aged individuals. Furthermore, the remaining CD141hi, GARP+ DCs from aged individuals were also deficient in inducing T regs. In summary, reduced response of aged DCs to RA enhances mucosal inflammation in the elderly, increasing their susceptibility to mucosal diseases.