Batf3-dependent dendritic cells in the renal lymph node induce tolerance against circulating antigens

Catherine Gottschalk, Vera Damuzzo, Janine Gotot, Richard A. Kroczek, Hideo Yagita, Kenneth M. Murphy, Percy A. Knolle, Isis Ludwig-Portugall, Christian Kurts

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Although the spleen is a major sitewhere 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 spleenwas 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.

Original languageEnglish
Pages (from-to)543-549
Number of pages7
JournalJournal of the American Society of Nephrology
Volume24
Issue number4
DOIs
StatePublished - Mar 29 2013

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