scholarly journals In vitro co-culture systems for studying molecular basis of cellular interaction between Aire-expressing medullary thymic epithelial cells and fresh thymocytes

Biology Open ◽  
2014 ◽  
Vol 3 (11) ◽  
pp. 1071-1082 ◽  
Author(s):  
Y. Yamaguchi ◽  
J. Kudoh ◽  
T. Yoshida ◽  
N. Shimizu
Keyword(s):  
Epithelial Cells ◽  
Molecular Basis ◽  
Cellular Interaction ◽  
Thymic Epithelial Cells ◽  
Culture Systems ◽  
Medullary Thymic Epithelial Cells

scholarly journals Autoimmune regulator act in synergism with thymocyte adhesion in the control of lncRNAs in medullary thymic epithelial cells

2021 ◽  
Author(s):  
Max J Duarte ◽  
Romario S Mascarenhas ◽  
Amanda F Assis ◽  
Pedro P Tanaka ◽  
Cesar A Speck-Hernandez ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Model Systems ◽  
Thymic Epithelial Cells ◽  
Large Set ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Autoimmune Regulator ◽  
Medullary Thymic Epithelial Cells

The autoimmune regulator (Aire) gene in medullary thymic epithelial cells (mTECs) encodes the AIRE protein, which interacts with its partners within the nucleus. This Aire complex induces stalled RNA Pol II on chromatin to proceed with transcription elongation of a large set of messenger RNAs and microRNAs. Considering that RNA Pol II also transcribes long noncoding RNAs (lncRNAs), we hypothesized that Aire might be implicated in the upstream control of this RNA species. To test this, we employed a loss-of-function approach in which Aire knockout mTECs were compared to Aire wild-type mTECs for lncRNA transcriptional profiling both in vitro and in vivo model systems. RNA sequencing enables the differential expression profiling of lncRNAs when these cells adhere in vitro to thymocytes or do not adhere to them as a way to test the effect of cell adhesion. Sets of lncRNAs that are unique and that are shared in vitro and in vivo were identified. Among these, we found the Aire-dependent lncRNAs as for example, Platr28, Ifi30, Morrbid, Malat1, and Xist. This finding represents the first evidence that Aire mediates the transcription of lncRNAs in mTECs. Microarray hybridizations enabled us to observe that temporal thymocyte adhesion modulates the expression levels of such lncRNAs as Morrbid, Xist, and Fbxl12o after 36h of adhesion. This finding shows the existence of a synergistic mechanism involving a link between thymocyte adhesion, Aire, and lncRNAs in mTECs that might be important for immune self-representation.

scholarly journals miR-155 exerts posttranscriptional control of autoimmune regulator (Aire) and tissue-restricted antigen genes in medullary thymic epithelial cells

2021 ◽  
Author(s):  
Pedro P Tanaka ◽  
Ernna H Oliveira ◽  
Mayara C Machado ◽  
Max J Duarte ◽  
Amanda F Assis ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Large Scale ◽  
Interaction Analysis ◽  
Luciferase Reporter ◽  
Thymic Epithelial Cells ◽  
Posttranscriptional Control ◽  
Autoimmune Regulator ◽  
Aire Gene ◽  
Medullary Thymic Epithelial Cells

Background: The autoimmune regulator (Aire) gene is critical for the appropriate establishment of central immune tolerance. As one of the main controllers of promiscuous gene expression in the thymus, Aire promotes the expression of thousands of downstream tissue-restricted antigen (TRA) genes, cell adhesion genes and transcription factor genes in medullary thymic epithelial cells (mTECs). Despite the increasing knowledge about the role of Aire as an upstream transcriptional controller, little is known about the mechanisms by which this gene could be regulated. Results: Here, we assessed the posttranscriptional control of Aire by miRNAs. The in silico miRNA-mRNA interaction analysis predicted thermodynamically stable hybridization between the 3UTR of Aire mRNA and miR-155, which was confirmed to occur within the cellular milieu through a luciferase reporter assay. This finding enabled us to hypothesize that miR-155 might play a role as an intracellular posttranscriptional regulator of Aire mRNA. To test this hypothesis, we transfected a murine mTEC cell line with a miR-155 mimic in vitro, which reduced the mRNA and protein levels of Aire. Moreover, large-scale transcriptome analysis showed the modulation of 311 downstream mRNAs, which included 58 TRA mRNAs. Moreover, miR-155 mimic-transfected cells exhibited a decrease in their chemotaxis property compared with control thymocytes. Conclusion: Overall, the results indicate that miR-155 may posttranscriptionally control Aire mRNA as well as a crucial process by which mTECs allow migration of thymocytes through chemotaxis.

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro

2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Progenitor Cells ◽  
Thymic Epithelial Cells ◽  
Erythroid Progenitor ◽  
Term Survival ◽  
Long Term Survival ◽  
Erythroid Progenitor Cells

scholarly journals Modulation of IGF2 Expression in the Murine Thymus and Thymic Epithelial Cells Following Coxsackievirus-B4 Infection

2021 ◽  
Vol 9 (2) ◽  
pp. 402
Author(s):  
Hélène Michaux ◽  
Aymen Halouani ◽  
Charlotte Trussart ◽  
Chantal Renard ◽  
Hela Jaïdane ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Line ◽  
Thymic Epithelial Cells ◽  
Altered Expression ◽  
Coxsackievirus B4 ◽  
Gene Coding ◽  
Self Tolerance ◽  
Stat3 Phosphorylation ◽  
The Stability

Coxsackievirus B4 (CV-B4) can infect human and murine thymic epithelial cells (TECs). In a murine TEC cell line, CV-B4 can downregulate the transcription of the insulin-like growth factor 2 (Igf2) gene coding for the self-peptide of the insulin family. In this study, we show that CV-B4 infections of a murine TEC cell line decreased Igf2 P3 promoter activity by targeting a region near the transcription start site; however, the stability of Igf2 transcripts remained unchanged, indicating a regulation of Igf2 transcription. Furthermore, CV-B4 infections decreased STAT3 phosphorylation in vitro. We also showed that mice infected with CV-B4 had an altered expression of Igf2 isoforms as detected in TECs, followed by a decrease in the pro-IGF2 precursor in the thymus. Our study sheds new light on the intrathymic regulation of Igf2 transcription during CV-B4 infections and supports the hypothesis that a viral infection can disrupt central self-tolerance to insulin by decreasing Igf2 transcription in the thymic epithelium.

Effects of 2,3,7,8-TCDD and PCB 126 on human thymic epithelial cells in vitro

2003 ◽  
Vol 77 (6) ◽  
pp. 358-364 ◽  
Author(s):  
Kai Riecke ◽  
André Schmidt ◽  
Ralf Stahlmann
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Pcb 126

scholarly journals Lymphotoxin β Receptor Regulates the Development of CCL21-Expressing Subset of Postnatal Medullary Thymic Epithelial Cells

2013 ◽  
Vol 190 (10) ◽  
pp. 5110-5117 ◽  
Author(s):  
Enkhsaikhan Lkhagvasuren ◽  
Mie Sakata ◽  
Izumi Ohigashi ◽  
Yousuke Takahama
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Medullary Thymic Epithelial Cells ◽  
Β Receptor

scholarly journals Human thymocytes bind to autologous and allogeneic thymic epithelial cells in vitro.

1986 ◽  
Vol 83 (17) ◽  
pp. 6588-6592 ◽  
Author(s):  
K. H. Singer ◽  
L. S. Wolf ◽  
D. F. Lobach ◽  
S. M. Denning ◽  
D. T. Tuck ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells

scholarly journals Foxn1 Regulates Lineage Progression in Cortical and Medullary Thymic Epithelial Cells But Is Dispensable for Medullary Sublineage Divergence

PLoS Genetics ◽  
2011 ◽  
Vol 7 (11) ◽  
pp. e1002348 ◽  
Author(s):  
Craig S. Nowell ◽  
Nicholas Bredenkamp ◽  
Stéphanie Tetélin ◽  
Xin Jin ◽  
Christin Tischner ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Medullary Thymic Epithelial Cells
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