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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.

Original publication

DOI

10.1084/jem.20102327

Type

Journal article

Journal

J Exp Med

Publication Date

14/02/2011

Volume

208

Pages

383 - 394

Keywords

Animals, Chemokines, Chemokines, C, Chemotaxis, Dacryocystitis, Dendritic Cells, Flow Cytometry, Fluorescent Antibody Technique, Image Processing, Computer-Assisted, Mice, Mice, Nude, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, Self Tolerance, T-Lymphocytes, Regulatory, Thymus Gland, Transcription Factors