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

作者全名："Liao, Weinian; Liu, Chaonan; Yang, Ke; Chen, Jun; Wu, Yiding; Zhang, Shuzhen; Yu, Kuan; Wang, Lisha; Ran, Li; Chen, Mo; Chen, Fang; Xu, Yang; Wang, Song; Wang, Fengchao; Zhang, Qian; Zhao, Jinghong; Ye, Lilin; Du, Changhong; Wang, Junping"

作者地址："[Liao, Weinian; Liu, Chaonan; Chen, Jun; Wu, Yiding; Zhang, Shuzhen; Yu, Kuan; Chen, Mo; Chen, Fang; Xu, Yang; Wang, Song; Wang, Fengchao; Du, Changhong; Wang, Junping] Army Med Univ, Chongqing Engn Res Ctr Nanomed, Inst Combined Injury, Coll Prevent Med,Mil Med Univ 3,State Key Lab Tra, Chongqing 400038, Peoples R China; [Yang, Ke; Ran, Li; Zhao, Jinghong] Army Med Univ, Kidney Ctr PLA, Xinqiao Hosp, Mil Med Univ 3,Dept Nephrol,Key Lab Prevent & Tre, Chongqing 400038, Peoples R China; [Wang, Lisha; Ye, Lilin] Army Med Univ, Inst Immunol, Mil Med Univ 3, Chongqing 400038, Peoples R China; [Zhang, Qian] Naval Med Univ, Nat Key Lab Med Immunol, Inst Immunol, Shanghai 200433, Peoples R China"

通信作者："Du, CH; Wang, JP (通讯作者)，Army Med Univ, Chongqing Engn Res Ctr Nanomed, Inst Combined Injury, Coll Prevent Med,Mil Med Univ 3,State Key Lab Tra, Chongqing 400038, Peoples R China.; Ye, LL (通讯作者)，Army Med Univ, Inst Immunol, Mil Med Univ 3, Chongqing 400038, Peoples R China."

来源：CELLULAR & MOLECULAR IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001072407000012

JCR分区：Q1

影响因子：21.8

年份：2023

卷号：20

期号：10

开始页：1216

结束页：1231

文献类型：Article

关键词：Hematopoietic stem cell; regulatory T cell; Aging

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."

基金机构："We thank Liting Wang for technical assistance with immunofluorescence. This study was supported by the Key Program of the National Natural Science Foundation of China (No. 81930090), the National Science Foundation for Distinguished Young Scholars of China"

基金资助正文："We thank Liting Wang for technical assistance with immunofluorescence. This study was supported by the Key Program of the National Natural Science Foundation of China (No. 81930090), the National Science Foundation for Distinguished Young Scholars of China (No. 81725019), and the National Natural Science Foundation of China (Nos. 82273571, 32171104, U22A20279, 81874256, and 81872556), Chongqing Natural Science Foundation (2023NSCQ-JQX0076)."