Laboratories of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Int J Med Sci. 2009 Dec 4;7(1):1-14. doi: 10.7150/ijms.7.1.
Age-associated thymic involution is characterized by decreased thymopoiesis, adipocyte deposition and changes in the expression of various thymic microenvironmental factors. In this work, we characterized the distribution of fat-storing cells within the aging thymus. We found an increase of unilocular adipocytes, ERTR7(+) and CCR5(+ )fat-storing multilocular cells in the thymic septa and parenchymal regions, thus suggesting that mesenchymal cells could be immigrating and differentiating in the aging thymus. We verified that the expression of CCR5 and its ligands, CCL3, CCL4 and CCL5, were increased in the thymus with age. Hypothesizing that the increased expression of chemokines and the CCR5 receptor may play a role in adipocyte recruitment and/or differentiation within the aging thymus, we examined the potential role for CCR5 signaling on adipocyte physiology using 3T3-L1 pre-adipocyte cell line. Increased expression of the adipocyte differentiation markers, PPARgamma2 and aP2 in 3T3-L1 cells was observed under treatment with CCR5 ligands. Moreover, 3T3-L1 cells demonstrated an ability to migrate in vitro in response to CCR5 ligands. We believe that the increased presence of fat-storing cells expressing CCR5 within the aging thymus strongly suggests that these cells may be an active component of the thymic stromal cell compartment in the physiology of thymic aging. Moreover, we found that adipocyte differentiation appear to be influenced by the proinflammatory chemokines, CCL3, CCL4 and CCL5.
年龄相关的胸腺萎缩的特征是胸腺生成减少、脂肪细胞沉积以及各种胸腺微环境因子表达的变化。在这项工作中，我们描述了衰老胸腺中储存脂肪细胞的分布。我们发现，胸腺隔和实质区域中，单房性脂肪细胞、ERTR7(+)和 CCR5(+)多房性脂肪储存细胞增加，因此表明间充质细胞可能在衰老的胸腺中迁移和分化。我们证实，随着年龄的增长，CCR5 及其配体 CCL3、CCL4 和 CCL5 在胸腺中的表达增加。假设趋化因子和 CCR5 受体的表达增加可能在衰老胸腺中的脂肪细胞募集和/或分化中发挥作用，我们使用 3T3-L1 前体脂肪细胞系研究了 CCR5 信号对脂肪细胞生理学的潜在作用。在 CCR5 配体处理下，3T3-L1 细胞中脂肪细胞分化标志物 PPARgamma2 和 aP2 的表达增加。此外，3T3-L1 细胞在体外表现出对 CCR5 配体的迁移能力。我们认为，衰老胸腺中表达 CCR5 的储存脂肪细胞的存在增加强烈表明，这些细胞可能是胸腺衰老生理中胸腺基质细胞区室的一个活跃组成部分。此外，我们发现脂肪细胞分化似乎受到促炎趋化因子 CCL3、CCL4 和 CCL5 的影响。
