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Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17129-33. doi: 10.1073/pnas.0906956106. Epub 2009 Sep 23.

CCR7-mediated migration of developing thymocytes to the medulla is essential for negative selection to tissue-restricted antigens.

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Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan.


Immature double-positive thymocytes are generated in the thymic cortex, and on positive selection, are induced to differentiate into mature single-positive thymocytes and relocate to the medulla. CCR7 is pivotal for cortex-to-medulla migration of positively selected thymocytes, and CCR7-mediated migration to the medulla is essential for establishing central tolerance, thereby, preventing tissue-specific autoimmunity. However, it was unclear how CCR7-mediated migration to the medulla affects the establishment of self-tolerance. Here, we show that the deletion of thymocytes specific for insulin-promoter-driven tissue-restricted antigens (TRAs) is significantly impaired in CCR7- or CCR7-ligand-deficient mice. These results indicate that CCR7-mediated migration to the medulla contributes to the negative selection of TRA-reactive thymocytes.

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