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.

与源自胚胎前体并在局部自我更新的表皮朗格汉斯细胞 (LC) 不同，粘膜 LC 出现并在整个生命过程中被循环骨髓 (BM) 前体取代。虽然表皮 LC 的独特生命周期与其数量的年龄依赖性减少有关，但衰老是否以及如何影响粘膜 LC 仍不清楚。着眼于牙龈 LCs，我们发现粘膜 LCs 随着年龄的增长而减少，但表现出与在老年表皮 LCs 中观察到的形态改变。老年小鼠牙龈而非表皮 LC 的减少是微生物群依赖性的；尽管如此，微生物群对牙龈 LC 的影响是间接的。我们接下来比较了年轻和年老的 BM 前体分化为粘膜 LC 的能力。混合 BM 嵌合体，以及分化培养物，表明与年轻的 BM 相比，老年 BM 具有完整的分化成 LC 的能力，即使不是更好的能力。这与在老年 BM 中检测到的较高百分比的粘膜 LC 前体、前 DC 和单核细胞一致。这些发现表明，虽然衰老与 LC 数量减少有关，但在粘膜屏障中控制这一过程的是利基而不是起源。