title: Dendritic Cells Coordinate the Development and Homeostasis of Organ-Specific Regulatory T Cells.
abstract: Although antigen recognition mediated by the T cell receptor (TCR) influences many facets of Foxp3(+) regulatory T (Treg) cell biology, including development and function, the cell types that present antigen to Treg cells in vivo remain largely undefined. By tracking a clonal population of Aire-dependent, prostate-specific Treg cells in mice, we demonstrated an essential role for dendritic cells (DCs) in regulating organ-specific Treg cell biology. We have shown that the thymic development of prostate-specific Treg cells required antigen presentation by DCs. Moreover, Batf3-dependent CD8α(+) DCs were dispensable for the development of this clonotype and had negligible impact on the polyclonal Treg cell repertoire. In the periphery, CCR7-dependent migratory DCs coordinated the activation of organ-specific Treg cells in the prostate-draining lymph nodes. Our results demonstrate that the development and peripheral regulation of organ-specific Treg cells are dependent on antigen presentation by DCs, implicating DCs as key mediators of organ-specific immune tolerance.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Leventhal
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Gilmore
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Julian M
authors.initials: JM
authors.lastname: Berger
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Saki
authors.initials: S
authors.lastname: Nishi
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Lee
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Malchow
authors.affiliation: Department of Medicine, Section of Hematology-Oncology, University of Chicago, IL 60637, USA.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Kline
authors.affiliation: Department of Medicine, Section of Hematology-Oncology, University of Chicago, IL 60637, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Kline
authors.affiliation: Department of Surgery, University of Chicago, IL 60637, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Vander Griend
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, IL 60637, USA.
authors.forename: Haochu
authors.initials: H
authors.lastname: Huang
authors.affiliation: Bioinformatics Core, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Socci
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA. Electronic address: psavage@bsd.uchicago.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Savage
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000276:immunology; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011467:Prostate / Q000166:cytology / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D054400:Receptors, CCR7 / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism; D000096927:AIRE Protein
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D054400:Receptors, CCR7; D012097:Repressor Proteins; D014157:Transcription Factors; D000096927:AIRE Protein; C409469:CD8 antigen, alpha chain; C515371:Ccr7 protein, mouse; C497965:Cd86 protein, mouse; C533289:SNFT protein, mouse