Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR7 signaling regulates fibrocytes in renal fibrosis

Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14098-103. doi: 10.1073/pnas.0511200103. Epub 2006 Sep 11.


Fibrocytes are a distinct population of bloodborne cells that share markers of leukocytes as well as mesenchymal cells. We hypothesized that CCR7-positive fibrocytes migrate into the kidney in response to secondary lymphoid tissue chemokine (SLC/CCL21) and contribute to renal fibrosis. To investigate this hypothesis, renal fibrosis was induced by unilateral ureteral obstruction in mice. A considerable number of fibrocytes dual-positive for CD45 and type I collagen (ColI) or CD34 and ColI infiltrated the interstitium, reaching a peak on day 7. Most fibrocytes were positive for CCR7, and CCL21/CCR7 blockade reduced the number of infiltrating fibrocytes. CCL21 and MECA79 dual-positive vessels were also detected in the interstitium. The blockade of CCL21/CCR7 signaling by anti-CCL21 antibodies reduced renal fibrosis, which was confirmed by a decrease in fibrosis in CCR7-null mice with concomitant reduction in renal transcripts of pro alpha1 chain of ColI and TGF-beta1. The number of F4/80-positive macrophages decreased along with renal transcripts of monocyte chemoattractant protein 1 (MCP-1/CCL2) after the blockade of CCL21/CCR7 signaling. These findings suggest that CCR7-positive fibrocytes infiltrate the kidney via CCL21-positive vessels, thereby contributing to the pathogenesis of renal fibrosis. Thus, the CCL21/CCR7 signaling of fibrocytes may provide therapeutic targets for combating renal fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / metabolism
  • Chemokine CCL2 / metabolism
  • Chemokine CCL21
  • Chemokines, CC / metabolism*
  • Fibrosis* / metabolism
  • Fibrosis* / pathology
  • Humans
  • Kidney* / cytology
  • Kidney* / metabolism
  • Kidney* / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Receptors, CCR7
  • Receptors, Chemokine / metabolism*
  • Signal Transduction / physiology*
  • Ureter / surgery


  • Antibodies
  • CCL21 protein, human
  • CCR7 protein, human
  • Ccl2 protein, mouse
  • Ccl21c protein, mouse
  • Ccr7 protein, mouse
  • Chemokine CCL2
  • Chemokine CCL21
  • Chemokines, CC
  • Receptors, CCR7
  • Receptors, Chemokine