scholarly journals Medullary Thymic Epithelial Cells and Central Tolerance in Autoimmune Hepatitis Development: Novel Perspective from a New Mouse Model

2015 ◽  
Vol 16 (1) ◽  
pp. 1980-2000 ◽  
Author(s):  
Konstantina Alexandropoulos ◽  
Anthony Bonito ◽  
Erica Weinstein ◽  
Olivier Herbin
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Autoimmune Hepatitis ◽  
Thymic Epithelial Cells ◽  
Central Tolerance ◽  
Medullary Thymic Epithelial Cells

Autonomous versus dendritic cell-dependent contributions of medullary thymic epithelial cells to central tolerance

2011 ◽  
Vol 32 (5) ◽  
pp. 188-193 ◽  
Author(s):  
Ludger Klein ◽  
Maria Hinterberger ◽  
Julia von Rohrscheidt ◽  
Martin Aichinger
Keyword(s):  
Dendritic Cell ◽  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Central Tolerance ◽  
Medullary Thymic Epithelial Cells

scholarly journals Post-Aire Medullary Thymic Epithelial Cells and Hassall’s Corpuscles as Inducers of Tonic Pro-Inflammatory Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Martti Laan ◽  
Ahto Salumets ◽  
Annabel Klein ◽  
Kerli Reintamm ◽  
Rudolf Bichele ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tolerance Induction ◽  
Convincing Evidence ◽  
Keratinocyte Differentiation ◽  
Thymic Epithelial Cells ◽  
Special Focus ◽  
Central Tolerance ◽  
Inflammatory Microenvironment ◽  
Medullary Thymic Epithelial Cells ◽  
Late Stages

While there is convincing evidence on the role of Aire-positive medullary thymic epithelial cells (mTEC) in the induction of central tolerance, the nature and function of post-Aire mTECs and Hassall’s corpuscles have remained enigmatic. Here we summarize the existing data on these late stages of mTEC differentiation with special focus on their potential to contribute to central tolerance induction by triggering the unique pro-inflammatory microenvironment in the thymus. In order to complement the existing evidence that has been obtained from mouse models, we performed proteomic analysis on microdissected samples from human thymic medullary areas at different differentiation stages. The analysis confirms that at the post-Aire stages, the mTECs lose their nuclei but maintain machinery required for translation and exocytosis and also upregulate proteins specific to keratinocyte differentiation and cornification. In addition, at the late stages of differentiation, the human mTECs display a distinct pro-inflammatory signature, including upregulation of the potent endogenous TLR4 agonist S100A8/S100A9. Collectively, the study suggests a novel mechanism by which the post-Aire mTECs and Hassall’s corpuscles contribute to the thymic microenvironment with potential cues on the induction of central tolerance.

scholarly journals Contrasting models of promiscuous gene expression by thymic epithelium

2005 ◽  
Vol 202 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Geoffrey O. Gillard ◽  
Andrew G. Farr
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Broad Spectrum ◽  
Alternative Model ◽  
Thymic Epithelial Cells ◽  
Central Tolerance ◽  
Thymic Epithelium ◽  
Medullary Thymic Epithelial Cells ◽  
Promiscuous Gene Expression ◽  
Self Antigens

Medullary thymic epithelial cells (mTECs) express a broad spectrum of tissue- restricted self-antigens (TRAs), which are required for the development of central tolerance. A new study suggests that TRA expression is a specialized property of terminally differentiated mTECs. However, as discussed here, an alternative model—whereby TRA expression is regulated by conserved developmental programs active in developing mTECs—may be equally plausible.

scholarly journals Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels

2005 ◽  
Vol 202 (1) ◽  
pp. 33-45 ◽  
Author(s):  
Jens Derbinski ◽  
Jana Gäbler ◽  
Benedikt Brors ◽  
Sascha Tierling ◽  
Sunitha Jonnakuty ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tolerance Induction ◽  
The Body ◽  
Thymic Epithelial Cells ◽  
Peripheral Tissues ◽  
Central Tolerance ◽  
Self Tolerance ◽  
Medullary Thymic Epithelial Cells ◽  
Thymic Stroma

The role of central tolerance induction has recently been revised after the discovery of promiscuous expression of tissue-restricted self-antigens in the thymus. The extent of tissue representation afforded by this mechanism and its cellular and molecular regulation are barely defined. Here we show that medullary thymic epithelial cells (mTECs) are specialized to express a highly diverse set of genes representing essentially all tissues of the body. Most, but not all, of these genes are induced in functionally mature CD80hi mTECs. Although the autoimmune regulator (Aire) is responsible for inducing a large portion of this gene pool, numerous tissue-restricted genes are also up-regulated in mature mTECs in the absence of Aire. Promiscuously expressed genes tend to colocalize in clusters in the genome. Analysis of a particular gene locus revealed expression of clustered genes to be contiguous within such a cluster and to encompass both Aire-dependent and –independent genes. A role for epigenetic regulation is furthermore implied by the selective loss of imprinting of the insulin-like growth factor 2 gene in mTECs. Our data document a remarkable cellular and molecular specialization of the thymic stroma in order to mimic the transcriptome of multiple peripheral tissues and, thus, maximize the scope of central self-tolerance.

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