2024-03-29T13:29:13Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/76962023-10-09T08:45:27Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2061
00925njm 22002777a 4500
dc
Rodriguez-Garcia, Mercedes
author
Ledgerwood, Levi
author
Yang, Yu
author
Xu, Jiangnan
author
Lal, Girdhari
author
Burrell, Bryna
author
Ma, Ge
author
Hashimoto, Daigo
author
Li, Yansui
author
Boros, Peter
author
Grisotto, Marcos
author
van Rooijen, Nico
author
Matesanz, Rafael
author
Tacke, Frank
author
Ginhoux, Florent
author
Ding, Yaozhong
author
Chen, Shu-Hsia
author
Randolph, Gwendalyn
author
Merad, Miriam
author
Bromberg, Jonathan S
author
Ochando, Jordi
author
2010-07
One of the main unresolved questions in solid organ transplantation is how to establish indefinite graft survival that is free from long-term treatment with immunosuppressive drugs and chronic rejection (i.e., the establishment of tolerance). The failure to achieve this goal may be related to the difficulty in identifying the phenotype and function of the cell subsets that participate in the induction of tolerance. To address this issue, we investigated the suppressive roles of recipient myeloid cells that may be manipulated to induce tolerance to transplanted hearts in mice. Using depleting mAbs, clodronate-loaded liposomes, and transgenic mice specific for depletion of CD11c+, CD11b+, or CD115+ cells, we identified a tolerogenic role for CD11b+CD115+Gr1+ monocytes during the induction of tolerance by costimulatory blockade with CD40L-specific mAb. Early after transplantation, Gr1+ monocytes migrated from the bone marrow into the transplanted organ, where they prevented the initiation of adaptive immune responses that lead to allograft rejection and participated in the development of Tregs. Our results suggest that mobilization of bone marrow CD11b+CD115+Gr1+ monocytes under sterile inflammatory conditions mediates the induction of indefinite allograft survival. We propose that manipulating the common bone marrow monocyte progenitor could be a useful clinical therapeutic approach for inducing transplantation tolerance.
J Clin Invest. 2010;120(7):2486-96
http://hdl.handle.net/20.500.12105/7696
20551515
10.1172/JCI41628
1558-8238
The Journal of clinical investigation
Monocytic suppressive cells mediate cardiovascular transplantation tolerance in mice