RRC ID 44308
Author Gottschalk C, Damuzzo V, Gotot J, Kroczek RA, Yagita H, Murphy KM, Knolle PA, Ludwig-Portugall I, Kurts C.
Title Batf3-dependent dendritic cells in the renal lymph node induce tolerance against circulating antigens.
Journal J Am Soc Nephrol
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.
Volume 24(4)
Pages 543-9
Published 2013-3-1
DOI 10.1681/ASN.2012101022
PII ASN.2012101022
PMID 23411785
PMC PMC3609142
MeSH 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
IF 9.274
Times Cited 28
Human and Animal Cells