Renal Dendritic Cells Adopt a Pro-Inflammatory Phenotype in Obstructive Uropathy to Activate T Cells but Do Not Directly Contribute to Fibrosis

Am J Pathol. 2012 Jan;180(1):91-103. doi: 10.1016/j.ajpath.2011.09.039. Epub 2011 Nov 8.

Abstract

Unilateral ureteral obstruction (UUO) is a well-characterized murine model of renal inflammation leading to fibrosis. Renal dendritic cells (DCs) constitute a significant portion of kidney leukocytes and may participate in local inflammation and have critical roles in antigen presentation. The heterogeneity in renal DC populations and surface marker overlap with monocytes/macrophages has made studying renal DCs difficult. These studies used CD11c-promoter driven reporter/depletion mice to study DCs in vivo. Studying early local inflammatory events (day 3 of UUO), in vivo multiphoton imaging of the intact kidney of CD11c reporter mice revealed more dendrite extensions and increased activity of renal DCs in real time. Phenotypic analysis suggested resident DC maturation in obstructed kidneys with increased CD11b and less F4/80 expressed. CD11b(hi) Gr-1(+) inflammatory DCs were also present in obstructed kidneys. T-cell receptor transgenic mice revealed enhanced antigen-presenting capacity of renal DCs after UUO, with increased antigen-specific T-cell proliferation in vivo and ex vivo. However, conditional DC ablation at days 0, 2, or 4 did not attenuate fibrosis or apoptosis 7 days after UUO, and depletion at 7 days did not alter outcomes at day 14. Therefore, after UUO, renal DCs exhibit inflammatory morphological and functional characteristics and are more effective antigen-presenting cells, but they do not directly contribute to tubulointerstitial damage and fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • CD11c Antigen / metabolism
  • Cytokines / biosynthesis
  • Dendritic Cells / metabolism
  • Dendritic Cells / physiology*
  • Fibrosis
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nephritis / pathology
  • Phenotype
  • T-Lymphocytes / immunology*
  • Ureter / pathology*
  • Ureteral Obstruction / immunology
  • Ureteral Obstruction / pathology*

Substances

  • CD11c Antigen
  • Cytokines