Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development

  • Yu Lei
    Division of Experimental Immunology, Institute for Genome Research 1 , 2
  • Naozumi Ishimaru
    Division of Experimental Immunology, Institute for Genome Research 1 , 2
  • Takashi Nagasawa
    Department of Immunobiology and Hematology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan 4
  • Michael R. Bösl
    Transgenic Core Facility, Max-Planck-Institute of Biochemistry, 82152 Martinsried, Germany 6
  • Lukas T. Jeker
    Laboratory of Pediatric Immunology, Center for Biomedicine, University of Basel and The University Children’s Hospital of Basel, 4058 Basel, Switzerland 5
  • Izumi Ohigashi
    Division of Experimental Immunology, Institute for Genome Research 1 , 2
  • Adiratna Mat Ripen
    Division of Experimental Immunology, Institute for Genome Research 1 , 2
  • Rene de Waal Malefyt
    Merck Research Laboratories, Palo Alto, CA 94304 7
  • Takeshi Nitta
    Division of Experimental Immunology, Institute for Genome Research 1 , 2
  • Georg A. Holländer
    Laboratory of Pediatric Immunology, Center for Biomedicine, University of Basel and The University Children’s Hospital of Basel, 4058 Basel, Switzerland 5
  • Yousuke Takahama
    Division of Experimental Immunology, Institute for Genome Research 1 , 2
  • Yoshio Hayashi
    Division of Experimental Immunology, Institute for Genome Research 1 , 2

Bibliographic Information

Published
2011-02-07
Resource Type
journal article
DOI
  • 10.1084/jem.20102327
  • 10.5451/unibas-ep29974
Publisher
Rockefeller University Press

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<jats:p>Dendritic cells (DCs) in the thymus (tDCs) are predominantly accumulated in the medulla and contribute to the establishment of self-tolerance. However, how the medullary accumulation of tDCs is regulated and involved in self-tolerance is unclear. We show that the chemokine receptor XCR1 is expressed by tDCs, whereas medullary thymic epithelial cells (mTECs) express the ligand XCL1. XCL1-deficient mice are defective in the medullary accumulation of tDCs and the thymic generation of naturally occurring regulatory T cells (nT reg cells). Thymocytes from XCL1-deficient mice elicit dacryoadenitis in nude mice. mTEC expression of XCL1, tDC medullary accumulation, and nT reg cell generation are diminished in Aire-deficient mice. These results indicate that the XCL1-mediated medullary accumulation of tDCs contributes to nT reg cell development and is regulated by Aire.</jats:p>

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