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

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.

Immunity. 2016 Mar 28 [Epub ahead of print]

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

Department of Pathology, University of Chicago, Chicago, IL 60637, USA., Department of Pathology, University of Chicago, Chicago, IL 60637, USA., Department of Pathology, University of Chicago, Chicago, IL 60637, USA., Department of Pathology, University of Chicago, Chicago, IL 60637, USA., Department of Pathology, University of Chicago, Chicago, IL 60637, USA., Department of Pathology, University of Chicago, Chicago, IL 60637, USA., Department of Medicine, Section of Hematology-Oncology, University of Chicago, IL 60637, USA., Department of Medicine, Section of Hematology-Oncology, University of Chicago, IL 60637, USA., Department of Surgery, University of Chicago, IL 60637, USA., Department of Medicine, Section of Rheumatology, University of Chicago, IL 60637, USA., Bioinformatics Core, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA., Department of Pathology, University of Chicago, Chicago, IL 60637, USA.