IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses

Immunity. 2013 May 23;38(5):970-83. doi: 10.1016/j.immuni.2013.04.011.


Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24(+)CD64(-) DCs and contaminating CSF-1R-dependent CD24(-)CD64(+) macrophages. Functionally, loss of CD24(+)CD11b(+) DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24(+)CD11b(+) DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspergillus fumigatus / immunology*
  • CD11b Antigen / metabolism
  • CD24 Antigen / metabolism
  • Cell Differentiation / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Humans
  • Interferon Regulatory Factors / metabolism*
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / metabolism*
  • Interleukin-23 / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Macrophages / metabolism
  • Mice
  • Receptors, IgG / metabolism
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / immunology
  • Th17 Cells / metabolism*
  • fms-Like Tyrosine Kinase 3 / metabolism


  • CD11b Antigen
  • CD24 Antigen
  • Interferon Regulatory Factors
  • Interleukin-17
  • Interleukin-23
  • Receptors, IgG
  • interferon regulatory factor-4
  • Flt3 protein, mouse
  • fms-Like Tyrosine Kinase 3

Associated data

  • GEO/GSE46680