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Publication : Aire Controls in <i>Trans</i> the Production of Medullary Thymic Epithelial Cells Expressing Ly-6C/Ly-6G.

First Author  Morimoto J Year  2018
Journal  J Immunol Volume  201
Issue  11 Pages  3244-3257
PubMed ID  30389776 Mgi Jnum  J:267758
Mgi Id  MGI:6258109 Doi  10.4049/jimmunol.1800950
Citation  Morimoto J, et al. (2018) Aire Controls in Trans the Production of Medullary Thymic Epithelial Cells Expressing Ly-6C/Ly-6G. J Immunol 201(11):3244-3257
abstractText  Medullary thymic epithelial cells (mTECs), which express a wide range of tissue-restricted Ags (TRAs), contribute to the establishment of self-tolerance by eliminating autoreactive T cells and/or inducing regulatory T cells. Aire controls a diverse set of TRAs within Aire-expressing cells by employing various transcriptional pathways. As Aire has a profound effect on transcriptomes of mTECs, including TRAs not only at the single-cell but also the population level, we suspected that Aire (Aire(+) mTECs) might control the cellular composition of the thymic microenvironment. In this study, we confirmed that this is indeed the case by identifying a novel mTEC subset expressing Ly-6 family protein whose production was defective in Aire-deficient thymi. Reaggregated thymic organ culture experiments demonstrated that Aire did not induce the expression of Ly-6C/Ly-6G molecules from mTECs as Aire-dependent TRAs in a cell-intrinsic manner. Instead, Aire(+) mTECs functioned in trans to maintain Ly-6C/Ly-6G(+) mTECs. Thus, Aire not only controls TRA expression transcriptionally within the cell but also controls the overall composition of mTECs in a cell-extrinsic manner, thereby regulating the transcriptome from mTECs on a global scale.
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