Effect of Granulocyte-Macrophage Colony-Stimulating Factor on the Generation of Epidermal Langerhans Cells

Abstract

The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) and Flt3 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 rate of LC recovery after depletion following lipopolysaccharide (LPS) treatment. The density of LC was determined by counting following IA-specific immunofluorescent staining of epidermal sections from mouse ears. LC levels were compared in beta common chain receptor null (beta c(-/-)) 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 beta c(-/-) mice but unchanged in Flt3 ligand-injected mice. Application of LPS to the ears of control BL/6 mice led to an approximately 70% reduction in LC 4 days later, with recovery beginning by day 8 and a return to normal levels by 2 weeks. This recovery was significantly delayed in beta c(-/-) mice and unchanged in Flt3 ligand-injected mice. These results suggest that GM-CSF (but not Flt3 ligand) enhances recruitment/maturation of LC even though GM-CSF is not essential for their formation.

Flk2+ myeloid progenitors are the main source of Langerhans cells

“…In addition, FL expands but does not accelerate splenic DC generation from progenitors, therefore FL administration should have no direct effect on LC recovery after UV light-induced inflammation, which is also in accordance with previous data reporting no effect on LC recovery after LPS-induced depletion. 38 We have shown before that splenic DC numbers derived from either CMPs or CLPs increase relative to the percentage of Flk2 ϩ cells within the progenitor population, but independent of their lineage origin. 28 It is therefore likely that in vivo FL administration has the same promoting effects on CMPs and CLPs during LC development in vivo as observed for conventional splenic DCs, with the exception that total LC numbers in the epidermis are not affected by FL.…”

“…In contrast to splenic and thymic DC populations, a direct effect of FL administration on LC development is difficult to determine in vivo, as FL injections do not increase total LC numbers in vivo, 38 which is most likely due to limited numbers of available LC niches in the epidermis. In addition, FL expands but does not accelerate splenic DC generation from progenitors, therefore FL administration should have no direct effect on LC recovery after UV light-induced inflammation, which is also in accordance with previous data reporting no effect on LC recovery after LPS-induced depletion.…”

Adult pulmonary Langerhans’ cell histiocytosis

“…The epithelial micro-environment is essential to LC recruitment and differentiation, in particular through local secretion of GM-CSF, TGF-b and the CC chemokine CCL20 (macrophage inflammatory protein (MIP)-3a) [51,84,85,[93][94][95][96][97][98][99][100][101][102]. Other factors, such as the expression of E-cadherin by both epithelial cells and LCs, are important for the tissue homing of these cells [103][104][105].…”

“…Interestingly, abundant GM-CSF production has also been found in skin LCH lesions, and the LCs in these lesions expressed the GM-CSF receptor [117]. In addition, intradermal injection of GM-CSF into patients with leprosy is associated with accumulation of numerous LCs at the injection site, and skin from transgenic animals that overexpress the GM-CSF gene contains far more epidermal LCs than skin from control animals [95,118,119]. Finally, GM-CSF transfection into the lung of mice promotes the differentiation and activation of a myeloid DC population, primarily by acting on macrophages during pulmonary immune responses [120].…”

Intercourse and ART Success Rates

“…Induction of GM-CSF and IL-6 in the cervical tissues would influence the activation status of local antigen-presenting cells, programming phenotypes that impact the ensuing response to antigens processed by those cells (36)(37)(38)(39). The significance of these two cytokines being preferentially expressed in the ectocervix is consistent with this tissue being the primary site for female 'sampling' of paternal antigens.…”