老年小鼠树突状细胞的再生。
Regeneration of dendritic cells in aged mice.
机构信息
The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia.
出版信息
Cell Mol Immunol. 2010 Mar;7(2):108-15. doi: 10.1038/cmi.2009.114. Epub 2010 Feb 1.
Age-related thymic involution causes a decreased output of thymocytes from the thymus, thereby resulting in impairment of T cell-mediated immunity. While alterations in the T cell and non-haematopoietic stromal compartments have been described, the effects of thymic involution on thymic dendritic cells (DC) are not clearly known. Thymic DC play an essential role in shaping T cell-mediated immune responses by deleting self-reactive thymocytes to establish central tolerance and by inducing regulatory T-cell (Treg) development. It is therefore important to assess the prevalence of and alterations to thymic DC with age, as this may impact on their function. We assessed the numbers and proportions of the three distinct subsets of thymic DC in ageing mice, and showed that these subsets are differentially regulated. This is expected as thymic DC subsets have different origins of development. We further assessed the responses of thymic DC in a regenerative environment, such as that induced by sex-steroid ablation (SSA), and clearly showed that, consistent with global thymus regrowth, all three DC populations increased in numbers and regained their relative proportions to thymocytes after an initial lag period. These findings are important for the clinical translation of thymic regenerative approaches, and indicate that SSA facilitates the maintenance of critical processes such as negative selection and Treg induction through promoting thymic DC regeneration.
年龄相关的胸腺萎缩导致胸腺中胸腺细胞的输出减少,从而导致 T 细胞介导的免疫受损。虽然已经描述了 T 细胞和非造血基质细胞区室的改变,但胸腺内树突状细胞 (DC) 的变化尚不清楚。胸腺 DC 通过删除自身反应性的胸腺细胞以建立中枢耐受,以及通过诱导调节性 T 细胞 (Treg) 的发育,在塑造 T 细胞介导的免疫反应中发挥着重要作用。因此,评估胸腺 DC 随年龄的变化和改变非常重要,因为这可能会影响其功能。我们评估了衰老小鼠中三种不同的胸腺 DC 亚群的数量和比例,并表明这些亚群受到不同的调节。这是意料之中的,因为胸腺 DC 亚群具有不同的发育起源。我们进一步评估了在再生环境(如性激素消融 (SSA) 诱导的环境)中胸腺 DC 的反应,并清楚地表明,与整个胸腺的再生一致,所有三种 DC 群体的数量增加,并在初始延迟期后恢复其与胸腺细胞的相对比例。这些发现对于胸腺再生方法的临床转化很重要,并表明 SSA 通过促进胸腺 DC 的再生来促进负选择和 Treg 诱导等关键过程的维持。