Effect of granulocyte-macrophage colony-stimulating factor on the generation of epidermal Langerhans cells

The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) and F lt3 ligand in the in vivo development of Langerhans cells (LC) was assessed , considering both the steady-state levels of LC in the epidermis and the r ate of LC recovery after depletion following lipopolysaccharide (LPS) treat ment. The density of LC was determined by counting following IA-specific im munofluorescent staining of epidermal sections from mouse ears, LC levels w ere compared in beta common chain receptor null (betac(-/-)) mice that fail to respond to GM-CSF interleukin-5 (IL-5), in GM-CSF transgenic mice with elevated GM-CSF levels, and in mice given daily injections of Flt3 ligand. In the steady state, LC levels were increased in GM-CSF transgenic mice and present at reduced levels in betac(-/-) mice but unchanged in Flt3 ligand- injected mice. Application of LPS to the ears of control BL/6 mice led to a n approximately 70% reduction in LC 4 days later, with recovery beginning b y day 8 and a return to normal levels by 2 weeks. This recovery was signifi cantly delayed in betac(-/-) mice and unchanged in Flt3 ligand-injected mic e. These results suggest that GM-CSF (but not Flt3 ligand) enhances recruit ment/maturation of LC even though GM-CSF is not essential for their formati on.