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

作者：Lei, Yu; Ripen, Adiratna Mat; Ishimaru, Naozumi; Ohigashi, Izumi; Nagasawa, Takashi; Jeker, Lukas T.; Boesl, Michael R.; Hollaender, Georg A.; Hayashi, Yoshio; Malefyt, Rene de Waal; Nitta, Takeshi; Takahama, Yousuke^*

来源：Journal of Experimental Medicine, 2011, 208(2): 383-394.

DOI：10.1084/jem.20102327

• PROMISCUOUS GENE-EXPRESSION
• CENTRAL TOLERANCE
• EPITHELIAL-CELLS
• NEGATIVE SELECTION
• DEVELOPING THYMOCYTES
• ANTIGEN PRESENTATION
• CLONAL DELETION
• LYMPHOID ORGANS
• TRANSGENIC MICE
• SELF-TOLERANCE

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.

• 出版日期2011-2-14
• 单位重庆医科大学