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Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance

ABSTRACT: Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance

PROVIDER: PRJNA1016559 | ENA |

REPOSITORIES: ENA

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Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance

Project description:Medullary thymic epithelial cells (mTECs) are essential for the establishment of self-tolerance in T cells. Promiscuous gene expression by a subpopulation of mTECs regulated by nuclear protein Aire contributes to the display of self-genomic products to newly generated T cells. Recent reports have highlighted additional self-antigen-displaying mTEC subpopulations; namely, Fezf2-expressing mTECs and a mosaic of self-mimetic mTECs including thymic tuft cells. In addition, a functionally different subset of mTECs produces chemokine CCL21 that attracts developing thymocytes to the medullary region. Here we report that CCL21+ mTECs and Aire+ mTECs non-redundantly cooperate to direct self-tolerance to prevent autoimmune pathology by optimizing the deletion of self-reactive T cells and the generation of regulatory T cells. We also detected a cooperation for self-tolerance between Aire and Fezf2, which unexpectedly regulates thymic tuft cells. Our results indicate an indispensable interplay among functionally diverse mTECs for the establishment of central self-tolerance.

2024-03-08 | GSE243180 | GEO

Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance II

2024-04-18 | GSE244501 | GEO

Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance II

Project description:Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance II

| PRJNA1023277 | ENA

ATAC-seq profiling of medullary thymic epithelial cells from wildtype and Kat7-knockout mice

Project description:Thymic epithelial cells govern thymic T lymphocyte differentiation and selection. Medullary TECs (mTECs) facilitate the negative selection of self-reactive thymocytes and the differentiation of FOXP3+ regulatory T cells. Medullary TECs are also distinctive for their “promiscuous” gene expression, transcribing thousands of peripheral tissue genes (PTG) that are otherwise only expressed highly in one or two other organs. Much of this PTG expression by mTECs is controlled by the autoimmune regulator, AIRE. To probe the mechanism by which KAT7 promotes AIRE function, we performed ATAC-seq to compare chromatin accessibility in MHCII-high medullary thymic epithelial cells from Kat7-knockout and wildtype mice.

2021-12-21 | GSE188868 | GEO

Silencing of C2TA reveals the autonomous role of medullary thymic epithelial cells in central CD4 T cell tolerance

Project description:[original title] Tissue-specific silencing of C2TA reveals the autonomous role of medullary thymic epithelial cells in central CD4 T cell tolerance. Medullary thymic epithelial cells (mTECs) serve an essential function in central tolerance through expressing peripheral tissue-antigens. Because these antigens may be transferred to and presented by Dendritic Cells, it is unclear whether, besides being an ‘antigen reservoir’, mTECs also fulfill a critical antigen presenting cellfunction. We found that reducing MHC class II-levels on mTECs through transgenic expression of a C2TA-specific ‘designer miRNA’ resulted in an enlarged polyclonal CD4 single-positive compartment. Less CD4+ thymocytes specific for model-antigens expressed in mTECs were deleted, whereas more antigen-specific Foxp3+ regulatory T cells (Treg) emerged. Our data suggest a substantial autonomous contribution of mTECs to both dominant and recessive mechanisms of CD4 T cell tolerance and support an avidity model of Treg development versus deletion.

2010-02-11 | GSE20276 | GEO

Single cell RNA-seq of medullary thymic epithelial cells (mTEC)

Project description:10x sequencing of TSPAN8+, GP2+ or Unselected medullary thymic epithelial cells (mTEC) isolated from female C57BL/6, BALB/c, and C57BL/6 x BALB/c F1 mice with the intent to identify co-expression patterns in promiscuously expressed genes in individual mTEC.

2019-10-17 | E-MTAB-8105 | biostudies-arrayexpress

Lymphtoxin pathway effects on thymic medullary epithelial cells

Project description:We compared gene expression profiles of lymphotoxin alpha- and lymphtoxin beta receptor-deficient thymic medullary epithelial cells with their wild-type littermates, as well as with Aire-deficient and wild-type littermates. This was done in order to determine whether there was overlap in the effects of lymphotoxin and aire. Keywords: genetic modification

2007-10-23 | GSE8563 | GEO

Comparison of ectopic gene expression in Cdx1+/+ and Cdx1-/- thymic medullary epithelial cells

Project description:We have found that Cdx1 can promote ectopic gene expression in thymic epithelial cells. We isolated MHCIIhi CD80hi medullary thymic epithelial cells from Cdx1-/- and Cdx1+/+ and compare gene expression between the two subsets, also in the context of Cdx1-mediated changes in intestinal epithelial cells.

2018-05-01 | GSE68880 | GEO

mRNA expression profile of medullary thymic epithelial cells - mTECs - from pre-diabetic NOD mice

Project description:The oligo microarrays were used to determine mRNA expression profiles of medullary thymic epithelial cells (mTECs) isolated from thymus of pre-diabetic NOD mice.

2012-08-11 | E-MEXP-3358 | biostudies-arrayexpress

Transcriptome diversity in human medullary thymic epithelial cells

Project description:Transcriptome diversity in human medullary thymic epithelial cells

| PRJNA832748 | ENA