Distinct Murine Mucosal Langerhans Cell Subsets Develop from Pre-dendritic Cells and Monocytes

Immunity. 2015 Aug 18;43(2):369-81. doi: 10.1016/j.immuni.2015.06.017. Epub 2015 Jul 28.


Langerhans cells (LCs) populate the mucosal epithelium, a major entry portal for pathogens, yet their ontogeny remains unclear. We found that, in contrast to skin LCs originating from self-renewing radioresistant embryonic precursors, oral mucosal LCs derive from circulating radiosensitive precursors. Mucosal LCs can be segregated into CD103(+)CD11b(lo) (CD103(+)) and CD11b(+)CD103(-) (CD11b(+)) subsets. We further demonstrated that similar to non-lymphoid dendritic cells (DCs), CD103(+) LCs originate from pre-DCs, whereas CD11b(+) LCs differentiate from both pre-DCs and monocytic precursors. Despite this ontogenetic discrepancy between skin and mucosal LCs, the transcriptomic signature and immunological function of oral LCs highly resemble those of skin LCs but not DCs. These findings, along with the epithelial position, morphology, and expression of the LC-associated phenotype strongly suggest that oral mucosal LCs are genuine LCs. Collectively, in a tissue-dependent manner, murine LCs differentiate from at least three distinct precursors (embryonic, pre-DC, and monocytic) in steady state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • Blood Circulation
  • CD11b Antigen / metabolism
  • Cell Differentiation*
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Epithelium / immunology
  • Integrin alpha Chains / metabolism
  • Langerhans Cells / immunology*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Mannose-Binding Lectins / genetics
  • Mannose-Binding Lectins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / immunology*
  • Mouth Mucosa / immunology*
  • Organ Specificity
  • Skin / immunology
  • Transcriptome / immunology


  • Antigens, CD
  • Antigens, Surface
  • CD11b Antigen
  • Cd207 protein, mouse
  • Integrin alpha Chains
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • alpha E integrins

Associated data

  • GEO/GSE68789