Dendritic Cells Coordinate the Development and Homeostasis of Organ-Specific Regulatory T Cells

Daniel S Leventhal; Dana C Gilmore; Julian M Berger; Saki Nishi; Victoria Lee; Sven Malchow; Douglas E Kline; Justin Kline; Donald J Vander Griend; Haochu Huang; Nicholas D Socci; Peter A Savage

doi:10.1016/j.immuni.2016.01.025

Dendritic Cells Coordinate the Development and Homeostasis of Organ-Specific Regulatory T Cells

Immunity. 2016 Apr 19;44(4):847-59. doi: 10.1016/j.immuni.2016.01.025. Epub 2016 Mar 29.

Authors

Affiliations

¹ Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
² Department of Medicine, Section of Hematology-Oncology, University of Chicago, IL 60637, USA.
³ Department of Surgery, University of Chicago, IL 60637, USA.
⁴ Department of Medicine, Section of Rheumatology, University of Chicago, IL 60637, USA.
⁵ Bioinformatics Core, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
⁶ Department of Pathology, University of Chicago, Chicago, IL 60637, USA. Electronic address: [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

AIRE Protein
Animals
Antigen Presentation / immunology*
B7-1 Antigen / biosynthesis
B7-1 Antigen / genetics
B7-2 Antigen / biosynthesis
B7-2 Antigen / genetics
Basic-Leucine Zipper Transcription Factors / genetics*
Basic-Leucine Zipper Transcription Factors / immunology
CD8 Antigens / metabolism
Cell Differentiation / immunology
Cell Movement / immunology
Dendritic Cells / immunology*
Lymphocyte Activation / immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Prostate / cytology
Prostate / immunology*
Receptors, Antigen, T-Cell / immunology
Receptors, CCR7 / metabolism
Repressor Proteins / genetics*
Repressor Proteins / immunology
Self Tolerance / immunology*
T-Lymphocytes, Regulatory / cytology
T-Lymphocytes, Regulatory / immunology*
Transcription Factors / metabolism

Substances

B7-1 Antigen
B7-2 Antigen
Basic-Leucine Zipper Transcription Factors
CD8 Antigens
CD8 antigen, alpha chain
Ccr7 protein, mouse
Cd86 protein, mouse
Receptors, Antigen, T-Cell
Receptors, CCR7
Repressor Proteins
SNFT protein, mouse
Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding