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Protection against autoimmunity is driven by thymic epithelial cell-mediated regulation of Treg development

ABSTRACT: Thymic education of Tregs is superior to negative selection in the prevention of autoimmunity. To address this hypothesis, TCR repertoirs of thymic and peripheral Tcells (including Tregs) from conditional NIK KO and WT mice have been sequenced and compared.

ORGANISM(S): Mus musculus

PROVIDER: GSE174733 | GEO | 2021/11/18

REPOSITORIES: GEO

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Protection against autoimmunity is driven by thymic epithelial cell-mediated regulation of Treg development

Project description:Thymic education of Tregs is superior to negative selection in the prevention of autoimmunity. To address this hypothesis, TCR repertoires of thymic and peripheral Tcells (including Tregs) from conditional NIK KO and WT mice have been sequenced and compared.

2021-11-18 | GSE182535 | GEO

Aire suppresses CTLA-4 expression from thymic stroma to control autoimmunity

Project description:We show that thymic epithelial cells in the medulla (mTECs) that present self-antigens (self-Ags) to developing thymocytes for establishing immunological self-tolerance also express CTLA-4 if Aire, loss of which is responsible for the hereditary autoimmunity, is nonfunctional. Upon binding with its ligand, CD80 and CD86, expressed on thymic DCs, CTLA-4/ligand complex was internalized by Aire-deficient mTECs. This attenuated the ability of DCs to provide costimulatory signals and to present self-Ags, resulting in the reduced production of Tregs.

2022-03-21 | GSE155082 | GEO

Protection against autoimmunity is driven by thymic epithelial cell-mediated regulation of Treg development

Project description:Protection against autoimmunity is driven by thymic epithelial cell-mediated regulation of Treg development

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Protection against autoimmunity is driven by thymic epithelial cell-mediated regulation of Treg development

Project description:Protection against autoimmunity is driven by thymic epithelial cell-mediated regulation of Treg development

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DRAK2 alters IL-2 sensitivity and Treg development

Project description:Drak2¬-deficient (Drak2-/-) mice are resistant to multiple models of autoimmunity, yet effectively eliminate pathogens and tumors. Thus, DRAK2 is an ideal target to treat autoimmune diseases. However, the mechanisms by which DRAK2 contributes to autoimmunity, particularly type 1 diabetes (T1D), remain unresolved. Our data indicate that DRAK2 contributes to autoimmunity in multiple ways by regulating thymic Treg development and by impacting the sensitivity of conventional T cells to Treg-mediated suppression.

2023-02-09 | PXD037922 | Pride

Transcriptome analysis of thymic APC subsets, mTECs and thymic DCs in comparison to splenic DCs

Project description:Thymic antigen-presenting cells (APCs), including thymic dendritic cells (t-DCs) and medullary thymic epithelial cells (mTECs) have been described to play a critical role in thymic Treg generation. Our findings could show that both these thymic APCs can induce a more pronounced demethylation of Foxp3 and other Treg-specific epigenetic signature genes in developing Tregs when compared to splenic DCs. In order to elucidate the unique properties of thymic APCs, gene expression profiling was performed in comparison to splenic DCs. Transcriptome analysis of thymic APCs revealed differential expression of costimulatory molecules that could be involved in stable Treg generation. Importantly, both mTEC- and t-DC- induced alloantigen-specific Tregs displayed significantly higher efficacy in prolonging skin allograft acceptance when compared to alloantigen-specific Tregs generated by splenic DCs.

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Aire suppresses CTLA-4 expression from thymic stroma to control autoimmunity

Project description:Aire suppresses CTLA-4 expression from thymic stroma to control autoimmunity

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High TCR self-reactivity drives regulatory T cell function during tissue-specific autoimmunity

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Gene expression by Treg subsets

Project description:Thymic-derived natural T regulatory cells (nTregs) are characterized by functional and phenotypic heterogeneity. Recently, a small fraction of peripheral Tregs have been shown to express Klrg1, but it remains unclear the extent Klrg1 defines a unique Treg subset. Here we show that Klrg1+ Tregs represent a terminally differentiated Treg subset derived from Klrg1- Tregs. This subset is a recent antigen-responsive and a highly activated short-lived Treg population that expresses enhanced levels of Treg suppressive molecules and that preferentially resides within mucosal tissues. The development of Klrg1+ Tregs also requires extensive IL-2R signaling. This activity represents a distinct function for IL-2, independent from its contribution to Treg homeostasis and competitive fitness. These and other properties are analogous to terminally differentiated short-lived CD8+ T effector cells. Our findings suggest that an important pathway driving antigen-activated conventional T lymphocytes also operates for Tregs. Gene expression analysis was performed of this and other Treg subsets based on expression of CD62L, CD69, and Klrg1 to define the molecular properties of Klrg1+ Tregs and its relationship to other Treg subsets found in the peripheral immune tissues. Mice were euthanized, spleen cell preparations were made, and each Treg subset was isolated by FACS cell sorting. RNA was immediately prepared for processing.

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Single-cell RNA-seq of murine thymic Treg cell progenitors and mature Treg cells

Project description:We use single-cell RNA-seq to determine distinct selection phenotypes of 2 rare thymic Treg cell progenitors as well as mature thymic Treg cells

2018-12-31 | GSE123067 | GEO

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