Journal
MOLECULAR IMMUNOLOGY
Volume 72, Issue -, Pages 92-102Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2016.02.015
Keywords
Thymus; Aire; Chemokine; RANK; Lymphotoxin; TNF
Categories
Funding
- Centre of Excellence in Translational Medicine
- Estonian Research Council [IUT2-2]
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The differentiation and proper function of thymic epithelial cells (TECs) depend on various tumor necrosis factor superfamily (TNFSF) signals that are needed to maintain the thymic stromal microenvironment. Nevertheless, the direct transcriptional effects of these signals on TECs remain unclear. To address this issue, we stimulated murine embryonic thymus tissue with selected TNFSF ligands and performed a gene expression profiling study. We show that Aire expression is a direct and specific effect of RANKL stimulation, whereas LT beta and TNF alpha are major inducers of chemokines in the thymic stroma and we propose differential NF-kappa B binding as one possible cause of these gene expression patterns. Our work provides further insight into the complex molecular pathways that shape the thymic microenvironment and maintain central tolerance. (c) 2016 Elsevier Ltd. All rights reserved.
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