Upregulation of Heme Oxygenase-1 Endues Immature Dendritic Cells With More Potent and Durable Immunoregulatory Properties and Promotes Engraftment in a Stringent Mouse Cardiac Allotransplant Model

Frontiers in Immunology
Yue ZhaoGang Chen

Abstract

Heme oxygenase-1 (HO-1) is critical for the ability of immature dendritic cells (imDCs) to suppress T-cell responses. Induction of high HO-1 expression may markedly improve the tolerogenic capacity of imDCs. Here, we generated bone marrow-derived DCs (BMDCs) from BALB/c mice with low doses of GM-CSF and IL-4. The adherent BMDCs were obtained as imDCs. Upregulation of HO-1 in imDCs (HO-1hi-imDCs) was achieved by cobalt protoporphyrin treatment. HO-1hi-imDCs proved to be more maturation-resistant than conventional imDCs, with an enhanced ability to inhibit allogeneic T-cell proliferation stimulated by anti-CD3/CD28 antibodies. When donor-derived DC adoptive transfer was performed in a stringent mouse cardiac allotransplant model, the extent of graft prolongation observed with HO-1hi imDCs was superior to that obtained with conventional imDCs. T-cell activation and proliferation in cardiac allograft recipients was more strongly suppressed in the HO-1hi imDC transfusion group than that in the untreated imDC group. Furthermore, donor HO-1hi imDCs were able to maintain a status of high HO-1 expression and survived longer in the recipient spleens than did untreated imDCs after adoptive transfer. In vitro-generated HO-1hi imDCs had an ...Continue Reading

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Citations

Dec 6, 2018·Current Opinion in Organ Transplantation·Travis D HullJoren C Madsen
Apr 17, 2019·International Journal of Molecular Sciences·Julien PoguThomas Simon
Nov 10, 2020·Frontiers in Immunology·Weitao QueXiao-Kang Li
Oct 31, 2020·Frontiers in Immunology·Quan ZhuangYingzi Ming

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Methods Mentioned

BETA
ELISA
density gradient centrifugation
flow cytometry
FACS

Software Mentioned

GraphPad Prism
Cellquest Pro
GraphPad

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