Manisa City Hospital, Department of Allergy and Clinical Immunology, Manisa, Turkey.
Merkezefendi State Hospital, Department of Medical Biochemistry, Manisa, Turkey.
Cytokine. 2021 Feb;138:155367. doi: 10.1016/j.cyto.2020.155367. Epub 2020 Nov 19.
Mesenchymal stem cells (MSCs) are powerful immunomodulatory cells. The effects of the aging on these abilities of MSCs have not been adequately clarified. In this study, alterations in immunomodulatory abilities of MSCs caused by aging were investigated. For this, dental pulp (DP) MSCs and peripheral blood mononuclear cells (PBMCs) of elderly and young donors were co-cultured age-matched and cross. We detected that the effects of DP-MSCs on Th1 and Th2 cells and their specific cytokines IFN-γ and IL-4 are not affected by aging. However, we observed that young and elderly DP-MSCs have different effects on Th17 and Treg cells. Th17 frequencies of young and elderly PBMCs were significantly increased only by young DP-MSCs, in contrast, Treg frequencies were significantly increased by elderly DP-MSCs. IL-6, IL-17a and HGF levels of both young and elderly PBMCs showed a significant increase only by young DP-MSCs, but TGF-β levels were significantly increased only by elderly DP-MSCs. The oral cavity is home to a rich microflora. The interactions of dental tissues with this microflora can lead them to acquire different epigenetic modifications. Aging can affect the microflora composition of the oral cavity and change this process in different directions. According to our findings, DP-MSCs are effective cells in the regulation of CD4 T cells, and their effects on Th1 and Th2 cells were not affected by aging. However, pleiotropic molecules IL-6 and HGF expressions, which are important in dental and bone tissue regeneration, decreased significantly in elderly DP-MSCs. This situation may have indirectly made a difference in the modulation effects of young and elderly DP-MSCs on the Th17 and Treg cells.
间充质干细胞（MSCs）是具有强大免疫调节功能的细胞。衰老对这些细胞功能的影响尚未得到充分阐明。在这项研究中，研究了衰老对间充质干细胞免疫调节能力的改变。为此，对老年和年轻供体的牙髓（DP）MSC 和外周血单核细胞（PBMC）进行了年龄匹配和交叉共培养。我们发现 DP-MSCs 对 Th1 和 Th2 细胞及其特定细胞因子 IFN-γ 和 IL-4 的作用不受衰老影响。然而，我们观察到年轻和老年 DP-MSCs 对 Th17 和 Treg 细胞有不同的影响。年轻和老年 PBMC 的 Th17 频率仅被年轻 DP-MSCs 显著增加，相反，Treg 频率仅被老年 DP-MSCs 显著增加。年轻和老年 PBMC 的 IL-6、IL-17a 和 HGF 水平仅被年轻 DP-MSCs 显著增加，但 TGF-β 水平仅被老年 DP-MSCs 显著增加。口腔是丰富微生物群的家园。牙组织与这种微生物群的相互作用会导致它们获得不同的表观遗传修饰。衰老会影响口腔微生物群的组成，并使这一过程朝着不同的方向发展。根据我们的发现，DP-MSCs 是调节 CD4 T 细胞的有效细胞，其对 Th1 和 Th2 细胞的作用不受衰老影响。然而，在老年 DP-MSCs 中，重要的牙齿和骨骼组织再生多效分子 IL-6 和 HGF 的表达显著下降。这种情况可能间接地导致了年轻和老年 DP-MSCs 对 Th17 和 Treg 细胞的调节作用的差异。
