The Journal of Experimental Medicine
Fluorescence In Vivo Endomicroscopy
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Published online 20 November 2006 doi:10.1084/jem.20060667
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 12, 2627-2638
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ARTICLE

 Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men

Milena Bogunovic1, Florent Ginhoux1, Amy Wagers4, Martine Loubeau1, Luis M. Isola2, Lauren Lubrano1,2, Vesna Najfeld2, Robert G. Phelps3, Celia Grosskreutz2, Eilleen Scigliano2, Paul S. Frenette2, and Miriam Merad1,2

1 Department of Gene and Cell Medicine, 2 Department of Medicine, and 3 Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10029
4 Joslin Diabetes Center, Boston, MA 02215

CORRESPONDENCE Miriam Merad: Miriam.Merad{at}mssm.edu

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.

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.


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