Donor monocyte-derived macrophages promote human acute graft versus host disease
Autor: | Smeera Nair, Muzlifah Haniffa, Gary Reynolds, Xiao-Nong Wang, Merry Gunawan, Graham H. Jackson, Matthew Collin, A. J. Simpson, Amy Publicover, Kile Green, Venetia Bigley, Sarah Pagan, Urszula Cytlak, Laura Jardine, M. Pradnya, Christopher A. Lamb, Erin Hurst, Anna Long |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0303 health sciences
CD14 Monocyte Antigen presentation CD11c Biology medicine.disease 3. Good health 03 medical and health sciences 0302 clinical medicine Graft-versus-host disease medicine.anatomical_structure Antigen Immunology medicine Macrophage Myelopoiesis 030304 developmental biology 030215 immunology |
DOI: | 10.1101/787036 |
Popis: | Myelopoiesis is invariably present, and contributes to pathology, in animal models of graft versus host disease (GVHD). In humans, a rich inflammatory infiltrate bearing macrophage markers has also been described in histological studies. In order to determine the origin, functional properties and role in pathogenesis of these cells, we isolated single cell suspensions from acute cutaneous GVHD and subjected them to genotype, transcriptome and in vitro functional analysis. A donor-derived population of CD11c+CD14+ cells was the dominant population of all leukocytes in GVHD. Surface phenotype and nanostring gene expression profiling indicated the closest steady-state counterpart of these cells to be monocyte-derived macrophages. In GVHD, however, there was upregulation of monocyte antigens SIRPα and S100A8/9, and transcripts associated with leukocyte trafficking, pattern recognition, antigen presentation, and co-stimulation. Isolated GVHD macrophages stimulated greater proliferation and activation of allogeneic T cells, and secreted higher levels of inflammatory cytokines than their steady-state counterparts. In HLA-matched mixed leukocyte reactions, we also observed differentiation of activated macrophages with a similar phenotype. These exhibited cytopathicity to a cell line and mediated pathological damage to skin explants, independently of T cells. Together, these results define the origin, functional properties and potential pathogenic roles of human GVHD macrophages. |
Databáze: | OpenAIRE |
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