In this study, we explored dermal dendritic cell (DC) homeostasis in mice and humans both in the steady state and after hematopoietic cell transplantation. We discovered that dermal DCs proliferate in situ in mice and human quiescent dermis. In parabiotic mice with separate organs but shared blood circulation, the majority of dermal DCs failed to be replaced by circulating precursors for >6 mo. In lethally irradiated mice injected with donor congenic bone marrow (BM) cells, a subset of recipient DCs remained in the dermis and proliferated locally throughout life. Consistent with these findings, a large proportion of recipient dermal DCs remained in patients' skin after allogeneic hematopoietic cell transplantation, despite complete donor BM chimerism. Collectively, our results oppose the traditional view that DCs are nondividing terminally differentiated cells maintained by circulating precursors and support the new paradigm that tissue DCs have local proliferative properties that control their homeostasis in the steady state. Given the role of residual host tissue DCs in transplant immune reactions, these results suggest that dermal DC homeostasis may contribute to the development of cutaneous graft-versus-host disease in clinical transplantation.
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27 November 2006
Article|
November 20 2006
Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men
Milena Bogunovic,
Milena Bogunovic
1Department of Gene and Cell Medicine
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Florent Ginhoux,
Florent Ginhoux
1Department of Gene and Cell Medicine
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Amy Wagers,
Amy Wagers
4Joslin Diabetes Center, Boston, MA 02215
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Martine Loubeau,
Martine Loubeau
1Department of Gene and Cell Medicine
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Lauren Lubrano,
Lauren Lubrano
1Department of Gene and Cell Medicine
2Department of Medicine,
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Robert G. Phelps,
Robert G. Phelps
3Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10029
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Celia Grosskreutz,
Celia Grosskreutz
2Department of Medicine,
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Eilleen Scigliano,
Eilleen Scigliano
2Department of Medicine,
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Paul S. Frenette,
Paul S. Frenette
2Department of Medicine,
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Miriam Merad
Miriam Merad
1Department of Gene and Cell Medicine
2Department of Medicine,
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Milena Bogunovic
1Department of Gene and Cell Medicine
Florent Ginhoux
1Department of Gene and Cell Medicine
Amy Wagers
4Joslin Diabetes Center, Boston, MA 02215
Martine Loubeau
1Department of Gene and Cell Medicine
Luis M. Isola
2Department of Medicine,
Lauren Lubrano
1Department of Gene and Cell Medicine
2Department of Medicine,
Vesna Najfeld
2Department of Medicine,
Robert G. Phelps
3Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10029
Celia Grosskreutz
2Department of Medicine,
Eilleen Scigliano
2Department of Medicine,
Paul S. Frenette
2Department of Medicine,
Miriam Merad
1Department of Gene and Cell Medicine
2Department of Medicine,
CORRESPONDENCE Miriam Merad: [email protected]
Abbreviations used: allo-HCT, allogeneic hematopoietic cell transplantation; ATG, antithymocyte globulin; DLI, donor lymphocyte infusion; FISH, fluorescence in situ hybridization; GVHD, graft-versus-host disease; LC, Langerhans cell; TBI, total body irradiation.
Received:
March 27 2006
Accepted:
October 10 2006
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2006
J Exp Med (2006) 203 (12): 2627–2638.
Article history
Received:
March 27 2006
Accepted:
October 10 2006
Citation
Milena Bogunovic, Florent Ginhoux, Amy Wagers, Martine Loubeau, Luis M. Isola, Lauren Lubrano, Vesna Najfeld, Robert G. Phelps, Celia Grosskreutz, Eilleen Scigliano, Paul S. Frenette, Miriam Merad; Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men . J Exp Med 27 November 2006; 203 (12): 2627–2638. doi: https://doi.org/10.1084/jem.20060667
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