Langerhans cells renew in the skin throughout life under steady-state conditions.
Langerhans cells (LCs) are bone marrow (BM)-derived epidermal dendritic cells (DCs) that represent a critical immunologic barrier to the external environment, but little is known about their life cycle. Here, we show that in lethally irradiated mice that had received BM transplants, LCs of host origin remained for at least 18 months, whereas DCs in other organs were almost completely replaced by donor cells within 2 months. In parabiotic mice with separate organs, but a shared blood circulation, there was no mixing of LCs. However, in skin exposed to ultraviolet light, LCs rapidly disappeared and were replaced by circulating LC precursors within 2 weeks. The recruitment of new LCs was dependent on their expression of the CCR2 chemokine receptor and on the secretion of CCR2-binding chemokines by inflamed skin. These data indicate that under steady-state conditions, LCs are maintained locally, but inflammatory changes in the skin result in their replacement by blood-borne LC progenitors.
Merad
Miriam
M
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304, USA. meradm@stanford.edu
Manz
Markus G
MG
Karsunky
Holger
H
Wagers
Amy
A
Peters
Wendy
W
Charo
Israel
I
Weissman
Irving L
IL
Cyster
Jason G
JG
Engleman
Edgar G
EG
D000818:Animals; D001773:Blood Cells / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology* / Q000528:radiation effects; D002465:Cell Movement / Q000276:immunology* / Q000528:radiation effects; D007249:Inflammation / Q000276:immunology; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology; D051379:Mice; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000276:immunology*; D012867:Skin / Q000166:cytology* / Q000276:immunology / Q000528:radiation effects; D013234:Stem Cells / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine