CCR2(+)CD103(-) intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells

Mucosal Immunol. 2015 Mar;8(2):327-39. doi: 10.1038/mi.2014.70. Epub 2014 Aug 20.


The identification of intestinal macrophages (mφs) and dendritic cells (DCs) is a matter of intense debate. Although CD103(+) mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103(-) MPs remain controversial. We show here that intestinal CD103(-)CD11b(+) MPs can be separated clearly into DCs and mφs based on phenotype, gene profile, and kinetics. CD64(-)CD103(-)CD11b(+) MPs are classical DCs, being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6C(hi) monocytes. Surprisingly, a significant proportion of these CD103(-)CD11b(+) DCs express CCR2 and there is a selective decrease in CD103(-)CD11b(+) DCs in mice lacking this chemokine receptor. CCR2(+)CD103(-) DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by T cells in vitro, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a bona fide population of CCR2(+) DCs that is involved in priming mucosal T helper type 17 (Th17) responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Cell Differentiation*
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Immunophenotyping
  • Integrin alpha Chains / metabolism
  • Interferon Regulatory Factors / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-17 / biosynthesis
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / immunology*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Transgenic
  • Monocytes / immunology
  • Monocytes / metabolism
  • Phagocytes / immunology
  • Phagocytes / metabolism
  • Phenotype
  • Receptors, CCR2 / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*


  • Antigens, CD
  • Integrin alpha Chains
  • Interferon Regulatory Factors
  • Interleukin-17
  • Receptors, CCR2
  • alpha E integrins
  • interferon regulatory factor-4
  • Interleukin-12