Aged hematopoietic stem cells entrap regulatory T cells to create a prosurvival microenvironment

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外文摘要：Although DNA mutation drives stem cell aging,how mutation-accumulated stem cells obtain clonal advantage during aging remains poorly understood.Here,using a mouse model of irradiation-induced premature aging and middle-aged mice,we show that DNA mutation accumulation in hematopoietic stem cells(HSCs)during aging upregulates their surface expression of major histocompatibility complex class II(MHCII).MHCII upregulation increases the chance for recognition by bone marrow(BM)-resident regulatory T cells(Tregs),resulting in their clonal expansion and accumulation in the HSC niche.On the basis of the establishment of connexin 43(Cx43)-mediated gap junctions,BM Tregs transfer cyclic adenosine monophosphate(cAMP)to aged HSCs to diminish apoptotic priming and promote their survival via activation of protein kinase A(PKA)signaling.Importantly,targeting the HSC-Treg interaction or depleting Tregs effectively prevents the premature/physiological aging of HSCs.These findings show that aged HSCs use an active self-protective mechanism by entrapping local Tregs to construct a prosurvival niche and obtain a clonal advantage.

外文关键词：

Hematopoietic stem cellregulatory T cellAging

作者：

Weinian Liao、Chaonan Liu、Ke Yang、Jun Chen、Yiding Wu、Shuzhen Zhang、Kuan Yu、Lisha Wang、Li Ran、Mo Chen、Fang Chen、Yang Xu、Song Wang、Fengchao Wang、Qian Zhang、Jinghong Zhao、Lilin Ye、Changhong Du、Junping Wang

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作者单位：

State Key Laboratory of Trauma,Burns,and Combined Injury,Institute of Combined Injury,Chongqing Engineering Research Center for Nanomedicine,College of Preventive Medicine,Army Medical University(Third Military Medical University),400038 Chongqing,China

Department of Nephrology,The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing,Kidney Center of PLA,Xinqiao Hospital,Army Medical University(Third Military Medical University),400037 Chongqing,China

Institute of Immunology,Army Medical University(Third Military Medical University),400038 Chongqing,China

National Key Laboratory of Medical Immunology,Institute of Immunology,Naval Medical University,200433 Shanghai,China

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基金：

Key Program of the National Natural Science Foundation of ChinaNational Science Foundation for Distinguished Young Scholars of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaChongqing Natural Science Foundation

项目编号：

81930090817250198227357132171104U22A2027981874256818725562023NSCQ-JQX0076

出版年：

2023

DOI：

10.1038/s41423-023-01072-3

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(10)

参考文献量71