期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 20, 期 10, 页码 2686-2702出版社
WILEY
DOI: 10.1111/ajt.15934
关键词
alloantibody; animal models; murine; basic (laboratory) research; science; immunobiology; macrophage; monocyte biology; differentiation; maturation; rejection; antibody-mediated (AMR); translational research; science; vascular biology
资金
- National Institute of Allergy and Infectious Diseases [U19AI128913, PO1AI120944, RO1AI042819, RO1AI135201, U01AI124319]
- Jiangsu Provincial Medical Youth Talent [QNRC2016739]
- Science and Technology Development Program of Suzhou [SYS201601, CXTDB2017009, GSWS2019033]
- Jiangsu Provincial Key Medical Discipline [ZDXKA2016012]
- CTOT NanoString Core [UO1 AI063594]
HLA donor-specific antibodies (DSAs) binding to vascular endothelial cells of the allograft trigger inflammation, vessel injury, and antibody-mediated rejection (AMR). Accumulation of intragraft-recipient macrophages is a histological characteristic of AMR, which portends worse outcome. HLA class I (HLA I) DSAs enhance monocyte recruitment by activating endothelial cells and engaging Fc gamma Rs, but the DSA-activated donor endothelial influence on macrophage differentiation is unknown. In this study, we explored the consequence of DSA-activated endothelium on infiltrating monocyte differentiation. Here we show that cardiac allografts from murine recipients treated with MHC I DSA upregulated genes related to monocyte transmigration and Fc receptor stimulation. Human monocytes co-cultured with HLA I IgG-stimulated primary human endothelium promoted monocyte differentiation into CD68(+)CD206(+)CD163(+)macrophages (M(HLA I IgG)), whereas HLA I F(ab ')(2) stimulated endothelium solely induced higher CD206 (M(HLA I F(ab ')(2))). Both macrophage subtypes exhibited significant changes in discrete cytokines/chemokines and unique gene expression profiles. Cross-comparison of gene transcripts between murine DSA-treated cardiac allografts and human co-cultured macrophages identified overlapping genes. These findings uncover the role of HLA I DSA-activated endothelium in monocyte differentiation, and point to a novel, remodeling phenotype of infiltrating macrophages that may contribute to vascular injury.
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