2025年10月15日，纽约大学医学院Dan R. Littman团队在《自然》杂志发表论文，宣布他们发现了特定生态位的皮肤巨噬细胞损失促进皮肤毛细血管衰老。

本研究表明，随着时间的推移，毛细血管相关巨噬细胞（CAMs）选择性丢失，导致老年小鼠血管修复受损和组织完善程度降低。为了研究巨噬细胞在体内的行为，课题组研究人员在活体小鼠中使用活体双光子显微镜对皮肤毛细血管丛进行无创成像，毛细血管丛是一个空间明确的血管生态位，随着年龄的增长而变得稀疏和功能下降。

该课题组人员发现CAMs的丢失速度超过毛细血管的丢失速度，导致小鼠和人类的巨噬细胞血管壁龛缺陷。局部需要CAM吞噬活性来修复阻塞的毛细血管血流，使巨噬细胞缺陷小生境在稳态和损伤条件下选择性地脆弱。他们的研究表明，常驻巨噬细胞的稳态更新不像以前认为的那样精确调节。具体来说，邻近的巨噬细胞在没有损伤或增加生长因子（如集落刺激因子1 (CSF1)）的情况下不会增殖或重组以补偿巨噬细胞的损失。巨噬细胞更新的这些限制可能代表了组织衰老的早期和可靶向的贡献者。

研究人员表示，所有哺乳动物的器官都依赖于巨噬细胞群体来协调修复和促进组织特异性功能。功能不同的巨噬细胞群存在于离散的组织壁龛中，并通过局部增殖和单核细胞募集的结合得到补充。巨噬细胞丰度和功能的下降与年龄相关的病理有关，包括动脉粥样硬化、癌症和神经退行性疾病。然而，在衰老组织中协调巨噬细胞组织和补充的机制仍不清楚。

附：英文原文

Title: Niche-specific dermal macrophage loss promotes skin capillary ageing

Author: Mesa, Kailin R., OConnor, Kevin A., Ng, Charles, Salvatore, Steven P., Dolynuk, Alexandra, Lomeli, Michelle Rivera, Littman, Dan R.

Issue&Volume: 2025-10-15

Abstract: All mammalian organs depend on resident macrophage populations to coordinate repair and facilitate tissue-specific functions1,2,3. Functionally distinct macrophage populations reside in discrete tissue niches and are replenished through a combination of local proliferation and monocyte recruitment4,5. Declines in macrophage abundance and function have been linked to age-associated pathologies, including atherosclerosis, cancer and neurodegeneration6,7,8. However, the mechanisms that coordinate macrophage organization and replenishment within ageing tissues remain largely unclear. Here we show that capillary-associated macrophages (CAMs) are selectively lost over time, contributing to impaired vascular repair and reduced tissue perfusion in older mice. To investigate resident macrophage behaviour in vivo, we used intravital two-photon microscopy in live mice to non-invasively image the skin capillary plexus, a spatially well-defined vascular niche that undergoes rarefication and functional decline with age. We find that CAMs are lost at a rate exceeding capillary loss, resulting in macrophage-deficient vascular niches in both mice and humans. CAM phagocytic activity was locally required to repair obstructed capillary blood flow, leaving macrophage-deficient niches selectively vulnerable under homeostatic and injury conditions. Our study demonstrates that homeostatic renewal of resident macrophages is less precisely regulated than previously suggested9,10,11. Specifically, neighbouring macrophages do not proliferate or reorganize to compensate for macrophage loss without injury or increased growth factors, such as colony-stimulating factor 1 (CSF1). These limitations in macrophage renewal may represent early and targetable contributors to tissue ageing.

DOI: 10.1038/s41586-025-09639-y

Source: https://www.nature.com/articles/s41586-025-09639-y