Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.
J Exp Med. 2011 Feb 14;208(2):383-94. doi: 10.1084/jem.20102327. Epub 2011 Feb 7.
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.
胸腺树突状细胞（tDCs）主要积聚在髓质中，并有助于建立自身耐受。然而，tDCs 向髓质的积聚是如何被调控的以及如何参与自身耐受尚不清楚。我们发现趋化因子受体 XCR1 在 tDCs 中表达，而髓质胸腺上皮细胞（mTECs）表达配体 XCL1。XCL1 缺陷小鼠在 tDCs 的髓质积聚和自然发生的调节性 T 细胞（nTreg 细胞）的胸腺生成方面存在缺陷。XCL1 缺陷小鼠的胸腺细胞在裸鼠中引发泪腺炎。Aire 缺陷小鼠的 mTEC 表达 XCL1、tDC 向髓质的积聚和 nTreg 细胞的生成减少。这些结果表明，XCL1 介导的 tDCs 向髓质的积聚有助于 nTreg 细胞的发育，并受 Aire 调控。
