Monocytes in allo-HSCT with aged donors secrete IL-1/IL-6/TNF to increase the risk of GVHD and damage the aged HSCs
Xia Li,
Wanying Zhang,
Yanan Wang,
Chentao Li,
Yibo Wu,
Yifei Shang,
Haikun Lin,
Yufei Li,
Yufei Wang,
Xiangjun Zeng,
Zenan Cen,
Xiaoyu Lai,
Yi Luo,
Pengxu Qian,
He Huang
Affiliations
Xia Li
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Liangzhu Laboratory, 1369 West Wenyi Road, Hangzhou 311121, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, Zhejiang, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, Zhejiang, China
Wanying Zhang
Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Yanan Wang
Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Chentao Li
Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Yibo Wu
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Liangzhu Laboratory, 1369 West Wenyi Road, Hangzhou 311121, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, Zhejiang, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, Zhejiang, China
Yifei Shang
Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Haikun Lin
Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Yufei Li
Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Yufei Wang
Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Xiangjun Zeng
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Liangzhu Laboratory, 1369 West Wenyi Road, Hangzhou 311121, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, Zhejiang, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, Zhejiang, China
Zenan Cen
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Liangzhu Laboratory, 1369 West Wenyi Road, Hangzhou 311121, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, Zhejiang, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, Zhejiang, China
Xiaoyu Lai
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Liangzhu Laboratory, 1369 West Wenyi Road, Hangzhou 311121, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, Zhejiang, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, Zhejiang, China
Yi Luo
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Liangzhu Laboratory, 1369 West Wenyi Road, Hangzhou 311121, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, Zhejiang, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, Zhejiang, China; Corresponding author
Pengxu Qian
Liangzhu Laboratory, 1369 West Wenyi Road, Hangzhou 311121, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, Zhejiang, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, Zhejiang, China; Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China; Corresponding author
He Huang
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Liangzhu Laboratory, 1369 West Wenyi Road, Hangzhou 311121, Zhejiang, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, Zhejiang, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, Zhejiang, China; Corresponding author
Summary: Aging is considered a critical factor of poor prognosis in allogenic hemopoietic stem cell transplantation (allo-HSCT). To elucidate the underlying mechanisms, we comprehensively reintegrated our clinical data from patients after allo-HSCT and public single-cell transcriptomic profile from post-allo-HSCT and healthy individuals, demonstrating that old donors were more prone to acute GVHD (aGVHD) with pronounced inflammation accumulation and worse overall survival (OS). We also found the presence of inflammation-related CXCL2+ HSC subpopulation during aging with significantly enriched pro-inflammatory pathways. Shifting attention to the HSC microenvironment, we deciphered that IL-1/IL-6 and TRAIL (i.e., TNFSF10) ligand‒receptor pair serves as the crucial bridge between CD14/CD16 monocytes and hematopoietic stem/progenitor cells (HSPCs). The profound upregulation of these signaling pathways during aging finally causes HSC dysfunction and lineage-biased differentiation. Our findings provide the theoretical basis for achieving tailored GVHD management and enhancing allo-HSCT regimens efficacy for aged donors.
