Increased blood myeloid dendritic cells and dendritic cell-poietins in Langerhans cell histiocytosis

J Immunol. 2005 Mar 1;174(5):3067-71. doi: 10.4049/jimmunol.174.5.3067.


Langerhans cell histiocytosis (LCH), previously known as histiocytosis X, is a reactive proliferative disease of unknown pathogenesis. Current therapies are based on nonspecific immunosuppression. Because multiple APCs, including Langerhans cells and macrophages, are involved in the lesion formation, we surmised that LCH is a disease of myeloid blood precursors. We found that lin(-) HLA-DR(+)CD11c-+ precursors of dendritic cells, able to give rise to either Langerhans cells or macrophages, are significantly (p = 0.004) increased in the blood of LCH patients. The analysis of serum cytokines in 24 patients demonstrated significantly elevated levels of hemopoietic cytokines such as fms-like tyrosine kinase ligand (FLT3-L, a dendritic cell-mobilizing factor, approximately 2-fold) and M-CSF ( approximately 4-fold). Higher levels of these cytokines correlated with patients having more extensive disease. Serum levels of FLT3-L and M-CSF were highest in high risk patients with extensive skin and/or multisystem involvement. Finally, patients with bone lesions had relatively higher levels of M-CSF and of stem cell factor. Thus, early hemopoietic cytokines such as FLT3-L, stem cell factor, and M-CSF maybe relevant in LCH pathogenesis and might be considered as novel therapeutic targets.

Publication types

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

MeSH terms

  • Adult
  • Child
  • Cytokines / biosynthesis
  • Cytokines / blood
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology*
  • Hematopoietic Cell Growth Factors / biosynthesis
  • Hematopoietic Cell Growth Factors / blood*
  • Histiocytosis, Langerhans-Cell / blood*
  • Histiocytosis, Langerhans-Cell / drug therapy
  • Histiocytosis, Langerhans-Cell / immunology
  • Histiocytosis, Langerhans-Cell / pathology*
  • Humans
  • Leukocyte Count
  • Ligands
  • Macrophage Colony-Stimulating Factor / biosynthesis
  • Macrophage Colony-Stimulating Factor / blood
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / blood
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism*
  • Myeloid Cells / pathology*
  • Myeloid Progenitor Cells / immunology
  • Myeloid Progenitor Cells / metabolism
  • Myeloid Progenitor Cells / pathology
  • Pilot Projects
  • Stem Cell Factor / biosynthesis
  • Stem Cell Factor / blood


  • Cytokines
  • Hematopoietic Cell Growth Factors
  • Ligands
  • Membrane Proteins
  • Stem Cell Factor
  • flt3 ligand protein
  • Macrophage Colony-Stimulating Factor