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

iScience (Mar 2024)

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

Journal volume & issue: Vol. 27, no. 3
p. 109126

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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