著作: [西川 裕美子]/[西嶋 仁]/Matsumoto Minoru/[森本 純子]/[廣田 史子]/Takahashi Satoru/Luche Hervé/Fehring Hans Joerg/[毛利 安宏]/[松本 満]/Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program./[The Journal of Immunology]
(英) Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program.
(英) Understanding the cellular dynamics of Aire-expressing lineage(s) among medullary thymic epithelial cells (AEL-mTECs) is essential for gaining insight into the roles of Aire in establishment of self-tolerance. In this study, we monitored the maturation program of AEL-mTECs by temporal lineage tracing, in which bacterial artificial chromosome transgenic mice expressing tamoxifen-inducible Cre recombinase under control of the Aire regulatory element were crossed with reporter strains. We estimated that the half-life of AEL-mTECs subsequent to Aire expression was ∼7-8 d, which was much longer than that reported previously, owing to the existence of a post-Aire stage. We found that loss of Aire did not alter the overall lifespan of AEL-mTECs, inconsistent with the previous notion that Aire expression in medullary thymic epithelial cells (mTECs) might result in their apoptosis for efficient cross-presentation of self-antigens expressed by AEL-mTECs. In contrast, Aire was required for the full maturation program of AEL-mTECs, as exemplified by the lack of physiological downregulation of CD80 during the post-Aire stage in Aire-deficient mice, thus accounting for the abnormally increased CD80(high) mTECs seen in such mice. Of interest, increased CD80(high) mTECs in Aire-deficient mice were not mTEC autonomous and were dependent on cross-talk with thymocytes. These results further support the roles of Aire in the differentiation program of AEL-mTECs.
The Journal of Immunology([The American Association of Immunologists])
|年月日||必須||2014年 2月 10日|