title: Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development.
abstract: 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.
authors.affiliation: Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.forename: Adiratna Mat
authors.initials: AM
authors.lastname: Ripen
authors.forename: Naozumi
authors.initials: N
authors.lastname: Ishimaru
authors.forename: Izumi
authors.initials: I
authors.lastname: Ohigashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Lukas T
authors.initials: LT
authors.lastname: Jeker
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bösl
authors.forename: Georg A
authors.initials: GA
authors.lastname: Holländer
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Rene de Waal
authors.initials: Rde W
authors.lastname: Malefyt
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nitta
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Takahama
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology; D019744:Chemokines, C / Q000096:biosynthesis* / Q000235:genetics; D002633:Chemotaxis / Q000276:immunology; D003607:Dacryocystitis / Q000209:etiology / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017634:Self Tolerance / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D018925:Chemokines; D019744:Chemokines, C; D014157:Transcription Factors; D000096927:AIRE Protein; C486249:Xcl1 protein, mouse