Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men.
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.
Bogunovic
Milena
M
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Ginhoux
Florent
F
Wagers
Amy
A
Loubeau
Martine
M
Isola
Luis M
LM
Lubrano
Lauren
L
Najfeld
Vesna
V
Phelps
Robert G
RG
Grosskreutz
Celia
C
Scigliano
Eilleen
E
Frenette
Paul S
PS
Merad
Miriam
M
D000208:Acute Disease; D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000145:classification* / Q000166:cytology / Q000276:immunology / Q000528:radiation effects*; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000166:cytology* / Q000276:immunology* / Q000473:pathology