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

• Published in: Frontiers in immunology 2018-07, Vol.9, p.1515-1515
• Main Authors: Zhao, Yue, Jia, Yu, Wang, Lu, Chen, Song, Huang, Xia, Xu, Bingyang, Zhao, Guangyuan, Xiang, Ying, Yang, Jun, Chen, Gang
• Format: Article
• Language: English
• Subjects: dendritic cells; heart transplantation; heme oxygenase-1; Immunology; immunoregulation; mouse
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.01515

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-1 -imDCs) was achieved by cobalt protoporphyrin treatment. HO-1 -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-1 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-1 imDC transfusion group than that in the untreated imDC group. Furthermore, donor HO-1 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. -generated HO-1 imDCs had an enhanced tolerogenic capacity to modulate alloimmune responses both and , and thus may offer a novel antigen-specific and cost-effective strategy to induce transplant tolerance.