Langerhans Cells Renew in the Skin Throughout Life Under Steady-State Conditions

Nat Immunol. 2002 Dec;3(12):1135-41. doi: 10.1038/ni852. Epub 2002 Nov 4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Cells / cytology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Cell Differentiation / immunology*
  • Cell Differentiation / radiation effects
  • Cell Movement / immunology*
  • Cell Movement / radiation effects
  • Inflammation / immunology
  • Langerhans Cells / cytology*
  • Langerhans Cells / immunology
  • Mice
  • Receptors, CCR2
  • Receptors, Chemokine / immunology*
  • Skin / cytology*
  • Skin / immunology
  • Skin / radiation effects
  • Stem Cells / immunology
  • Stem Cells / radiation effects
  • Ultraviolet Rays

Substances

  • Ccr2 protein, mouse
  • Receptors, CCR2
  • Receptors, Chemokine