Niche-specific macrophage loss promotes skin capillary aging.

Kailin R Mesa, Kevin A O'Connor, Charles Ng, Steven P Salvatore, Alexandra Dolynuk, Michelle Rivera Lomeli, Dan R Littman
{"title":"Niche-specific macrophage loss promotes skin capillary aging.","authors":"Kailin R Mesa, Kevin A O'Connor, Charles Ng, Steven P Salvatore, Alexandra Dolynuk, Michelle Rivera Lomeli, Dan R Littman","doi":"10.1101/2023.08.25.554832","DOIUrl":null,"url":null,"abstract":"<p><p>All mammalian organs depend upon resident macrophage populations to coordinate repair processes and facilitate tissue-specific functions<sup>1-3</sup>. Recent work has established that functionally distinct macrophage populations reside in discrete tissue niches and are replenished through some combination of local proliferation and monocyte recruitment<sup>4,5</sup>. Moreover, decline in macrophage abundance and function in tissues has been shown to contribute to many age-associated pathologies, such as atherosclerosis, cancer, and neurodegeneration<sup>6-8</sup>. Despite these advances, the cellular mechanisms that coordinate macrophage organization and replenishment within an aging tissue niche remain largely unknown. Here we show that capillary-associated macrophages (CAMs) are selectively lost over time, which contributes to impaired vascular repair and tissue perfusion in older mice. To investigate resident macrophage behavior <i>in vivo</i>, we have employed intravital two-photon microscopy to non-invasively image in live mice the skin capillary plexus, a spatially well-defined model of niche aging that undergoes rarefication and functional decline with age. We find that CAMs are lost with age at a rate that outpaces that of capillary loss, leading to the progressive accumulation of capillary niches without an associated macrophage in both mice and humans. Phagocytic activity of CAMs was locally required to repair obstructed capillary blood flow, leaving macrophage-less niches selectively vulnerable to both homeostatic and injury-induced loss in blood flow. Our work demonstrates that homeostatic renewal of resident macrophages is not as finely tuned as has been previously suggested<sup>9-11</sup>. Specifically, we found that neighboring macrophages do not proliferate or reorganize sufficiently to maintain an optimal population across the skin capillary niche in the absence of additional cues from acute tissue damage or increased abundance of growth factors, such as colony stimulating factor 1 (CSF1). Such limitations in homeostatic renewal and organization of various niche-resident cell types are potentially early contributors to tissue aging, which may provide novel opportunities for future therapeutic interventions.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473701/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv : the preprint server for biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2023.08.25.554832","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

All mammalian organs depend upon resident macrophage populations to coordinate repair processes and facilitate tissue-specific functions1-3. Recent work has established that functionally distinct macrophage populations reside in discrete tissue niches and are replenished through some combination of local proliferation and monocyte recruitment4,5. Moreover, decline in macrophage abundance and function in tissues has been shown to contribute to many age-associated pathologies, such as atherosclerosis, cancer, and neurodegeneration6-8. Despite these advances, the cellular mechanisms that coordinate macrophage organization and replenishment within an aging tissue niche remain largely unknown. Here we show that capillary-associated macrophages (CAMs) are selectively lost over time, which contributes to impaired vascular repair and tissue perfusion in older mice. To investigate resident macrophage behavior in vivo, we have employed intravital two-photon microscopy to non-invasively image in live mice the skin capillary plexus, a spatially well-defined model of niche aging that undergoes rarefication and functional decline with age. We find that CAMs are lost with age at a rate that outpaces that of capillary loss, leading to the progressive accumulation of capillary niches without an associated macrophage in both mice and humans. Phagocytic activity of CAMs was locally required to repair obstructed capillary blood flow, leaving macrophage-less niches selectively vulnerable to both homeostatic and injury-induced loss in blood flow. Our work demonstrates that homeostatic renewal of resident macrophages is not as finely tuned as has been previously suggested9-11. Specifically, we found that neighboring macrophages do not proliferate or reorganize sufficiently to maintain an optimal population across the skin capillary niche in the absence of additional cues from acute tissue damage or increased abundance of growth factors, such as colony stimulating factor 1 (CSF1). Such limitations in homeostatic renewal and organization of various niche-resident cell types are potentially early contributors to tissue aging, which may provide novel opportunities for future therapeutic interventions.

Abstract Image

Abstract Image

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
小生境特异性巨噬细胞损失促进皮肤毛细血管老化。
所有哺乳动物器官都依赖于常驻巨噬细胞群体来协调修复过程并促进组织特异性功能1-3。最近的工作已经证实,功能不同的巨噬细胞群体存在于离散的组织小生境中,并通过局部增殖和单核细胞募集的某种组合进行补充4,5。此外,组织中巨噬细胞丰度和功能的下降已被证明与许多年龄相关的病理有关,如动脉粥样硬化、癌症和神经变性6-8。尽管取得了这些进展,但在衰老组织生态位内协调巨噬细胞组织和补充的细胞机制在很大程度上仍然未知。在这里,我们发现随着时间的推移,毛细血管相关巨噬细胞(CAM)选择性地丢失,这有助于老年小鼠的血管修复和组织灌注受损。为了研究体内常驻巨噬细胞的行为,我们使用活体内双光子显微镜对活体小鼠的皮肤毛细血管丛进行了非侵入性成像,这是一种空间明确的小生境衰老模型,随着年龄的增长,它会经历稀疏化和功能下降。我们发现,CAM随着年龄的增长而丢失的速度超过了毛细血管丢失的速度,导致小鼠和人类在没有相关巨噬细胞的情况下逐渐积累毛细血管小生境。局部需要CAM的吞噬细胞活性来修复阻塞的毛细血管血流,使无巨噬细胞的小生境选择性地易受稳态和损伤诱导的血流损失的影响。我们的工作表明,常驻巨噬细胞的稳态更新并不像之前所建议的那样精细9-11。具体而言,我们发现,在缺乏急性组织损伤或生长因子(如集落刺激因子1(CSF1))丰度增加的额外提示的情况下,相邻巨噬细胞不能充分增殖或重组,从而在整个皮肤毛细血管生态位上维持最佳群体。这种在稳态更新和各种小众驻留细胞类型的组织方面的限制可能是组织衰老的早期因素,这可能为未来的治疗干预提供新的机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Meta-Analysis Reveals That Explore-Exploit Decisions are Dissociable by Activation in the Dorsal Lateral Prefrontal Cortex and the Dorsal Anterior Cingulate Cortex. Loop Catalog: a comprehensive HiChIP database of human and mouse samples. Anti-tumor immunity relies on targeting tissue homeostasis through monocyte-driven responses rather than direct tumor cytotoxicity. Lipid Transfer Proteins and PI4KIIα Initiate Nuclear p53-Phosphoinositide Signaling. Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1