The Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel.
Department of Periodontology, Faculty of Dental Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Mucosal Immunol. 2020 Sep;13(5):767-776. doi: 10.1038/s41385-020-0301-y. Epub 2020 May 26.
Unlike epidermal Langerhans cells (LCs) that originate from embryonic precursors and are self-renewed locally, mucosal LCs arise and are replaced by circulating bone marrow (BM) precursors throughout life. While the unique lifecycle of epidermal LCs is associated with an age-dependent decrease in their numbers, whether and how aging has an impact on mucosal LCs remains unclear. Focusing on gingival LCs we found that mucosal LCs are reduced with age but exhibit altered morphology with that observed in aged epidermal LCs. The reduction of gingival but not epidermal LCs in aged mice was microbiota-dependent; nevertheless, the impact of the microbiota on gingival LCs was indirect. We next compared the ability of young and aged BM precursors to differentiate to mucosal LCs. Mixed BM chimeras, as well as differentiation cultures, demonstrated that aged BM has intact if not superior capacity to differentiate into LCs than young BM. This was in line with the higher percentages of mucosal LC precursors, pre-DCs, and monocytes, detected in aged BM. These findings suggest that while aging is associated with reduced LC numbers, the niche rather than the origin controls this process in mucosal barriers.
与起源于胚胎前体并在局部自我更新的表皮朗格汉斯细胞 (LC) 不同，黏膜 LC 由循环骨髓 (BM) 前体产生并在整个生命周期中被替代。虽然表皮 LC 的独特生命周期与数量随年龄增长而减少有关，但衰老是否以及如何影响黏膜 LC 尚不清楚。我们专注于牙龈 LC 发现，黏膜 LC 随年龄增长而减少，但表现出与衰老表皮 LC 观察到的形态改变。在老年小鼠中，牙龈 LC 而不是表皮 LC 的减少依赖于微生物群；然而，微生物群对牙龈 LC 的影响是间接的。接下来，我们比较了年轻和老年 BM 前体分化为黏膜 LC 的能力。混合 BM 嵌合体以及分化培养表明，老年 BM 分化为 LC 的能力完整，如果不比年轻 BM 更好的话。这与在老年 BM 中检测到的更高比例的黏膜 LC 前体、前 DC 和单核细胞一致。这些发现表明，尽管衰老与 LC 数量减少有关，但在黏膜屏障中，是龛位而不是起源控制着这个过程。
