CCR7 is critically important for migration of dendritic cells in intestinal lamina propria to mesenteric lymph nodes

J Immunol. 2006 Jan 15;176(2):803-10. doi: 10.4049/jimmunol.176.2.803.


Although dendritic cells (DCs) located in the small intestinal lamina propria (LP-DCs) migrate to mesenteric lymph nodes (MLNs) constitutively, it is unclear which chemokines regulate their trafficking to MLNs. In this study we report that LP-DCs in unperturbed mice require CCR7 to migrate to MLNs. In vitro, LP-DCs expressing CCR7 migrated toward CCL21, although the LP-DCs appeared morphologically and phenotypically immature. In MLNs, DCs bearing the unique LP-DC phenotype (CD11chighCD8alphaintCD11blowalphaLlowbeta7high and CD11chighCD8alpha-CD11bhighalphaLlowbeta7high) were abundant in wild-type mice, but were markedly fewer in CCL19-, CCL21-Ser-deficient plt/plt mice and were almost absent in CCR7-deficient mice, indicating the critical importance of CCR7 in LP-DC trafficking to MLNs. Interestingly, CCR7+ DCs in MLNs with the unique LP-DC phenotype had numerous vacuoles containing cellular debris in the cytoplasm, although MLN-DCs themselves were poorly phagocytic, suggesting that the debris was derived from the LP, where the LP-DCs ingested apoptotic intestinal epithelial cells (IECs). Consistent with this, LP-DCs ingested IECs vigorously in vitro. By presenting IEC-associated Ag, the LP-DCs also induce T cells to produce IL-4 and IL-10. Collectively, these results strongly suggest that LP-DCs with unique immunomodulatory activities migrate to MLNs in a CCR7-dependent manner to engage in the presentation of IEC-associated Ags acquired in the LP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Apoptosis
  • Base Sequence
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation
  • Cell Movement / immunology
  • Cell Movement / physiology
  • Chemokine CCL21
  • Chemokines, CC / metabolism
  • DNA / genetics
  • Dendritic Cells / classification
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology*
  • Endocytosis
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Gene Expression
  • In Vitro Techniques
  • Interleukin-10 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Receptors, CCR7
  • Receptors, Chemokine / deficiency
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / physiology*


  • Ccl21c protein, mouse
  • Ccr7 protein, mouse
  • Chemokine CCL21
  • Chemokines, CC
  • Receptors, CCR7
  • Receptors, Chemokine
  • Interleukin-10
  • Interleukin-4
  • DNA