title: TNF superfamily members play distinct roles in shaping the thymic stromal microenvironment.
abstract: 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 LTβ and TNFα are major inducers of chemokines in the thymic stroma and we propose differential NF-κB 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.
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia. Electronic address: rudolf.bichele@ut.ee.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bichele
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
authors.forename: Kai
authors.initials: K
authors.lastname: Kisand
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
authors.forename: Pärt
authors.initials: P
authors.lastname: Peterson
authors.affiliation: Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
authors.forename: Martti
authors.initials: M
authors.lastname: Laan
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment; D020869:Gene Expression Profiling; D053259:Lymphotoxin beta Receptor / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D052002:NF-kappa B p50 Subunit / Q000096:biosynthesis / Q000235:genetics; D009924:Organ Culture Techniques; D053245:RANK Ligand / Q000235:genetics; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D053259:Lymphotoxin beta Receptor; D052002:NF-kappa B p50 Subunit; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; C073701:Nfkb1 protein, mouse
keywords: Aire; Chemokine; Lymphotoxin; RANK; TNF; Thymus