Batf3-dependent Dendritic Cells in the Renal Lymph Node Induce Tolerance Against Circulating Antigens

J Am Soc Nephrol. 2013 Mar;24(4):543-9. doi: 10.1681/ASN.2012101022. Epub 2013 Feb 14.

Abstract

Although the spleen is a major site where immune tolerance to circulating innocuous antigens occurs, the kidney also contributes. Circulating antigens smaller than albumin are constitutively filtered and concentrated in the kidney and reach the renal lymph node by lymphatic drainage, where resident dendritic cells (DCs) capture them and induce tolerance of specific cytotoxic T cells through unknown mechanisms. Here, we found that the coinhibitory cell surface receptor programmed death 1 (PD-1) on cytotoxic T cells mediates to their tolerance. Renal lymph node DCs of the CD8(+) XCR1(+) subset, which depend on the transcription factor Batf3, expressed the PD-1 cognate ligand PD-L1. Batf3-dependent DCs in the renal lymph node presented antigen that had been concentrated in the kidney and used PD-L1 to induce apoptosis of cytotoxic T cells. In contrast, T cell tolerance in the spleen was independent of PD-1, PD-L1, and Batf3. In summary, these results clarify how the kidney/renal lymph node system tolerizes the immune system against circulating innocuous antigens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / blood
  • Antigens / immunology*
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Immune Tolerance / immunology*
  • Kidney / immunology*
  • Kidney / metabolism
  • Lymph Nodes / immunology*
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Mutant Strains
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Antigens
  • Basic-Leucine Zipper Transcription Factors
  • Programmed Cell Death 1 Receptor
  • Repressor Proteins
  • SNFT protein, mouse