title: Batf3-dependent dendritic cells in the renal lymph node induce tolerance against circulating antigens.
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.
authors: Institutes of Molecular Medicine and Experimental Immunology, Rheinische Friedrich-Wilhelms-Universität, Sigmund Freud Strasse 25, 53105 Bonn, Germany.
authors: Catherine
authors: C
authors: Gottschalk
authors: Vera
authors: V
authors: Damuzzo
authors: Janine
authors: J
authors: Gotot
authors: Richard A
authors: RA
authors: Kroczek
authors: Hideo
authors: H
authors: Yagita
authors: Kenneth M
authors: KM
authors: Murphy
authors: Percy A
authors: PA
authors: Knolle
authors: Isis
authors: I
authors: Ludwig-Portugall
authors: Christian
authors: C
authors: Kurts
mesh_terms: D000818:Animals; D000941:Antigens / Q000097:blood / Q000276:immunology*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology*; D007668:Kidney / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D000941:Antigens; D050976:Basic-Leucine Zipper Transcription Factors; D061026:Programmed Cell Death 1 Receptor; D012097:Repressor Proteins; C533289:SNFT protein, mouse