Background: In order to become functionally competent but harmless mediators of the immune system, T cells undergo a strict educational program in the thymus, where they learn to discriminate between self and non-self. This educational program is, to a large extent, mediated by medullary thymic epithelial cells (mTECs) that have a unique capacity to express, and subsequently present a large fraction of body antigens. While the scope of promiscuously expressed genes by mTECs is well established, relatively little is known about the expression of variants that are generated by co- and post-transcriptional processes. Results: Our study reveals that in comparison to other cell types, mTECs display significantly higher levels of alternative splicing, as well as A-to-I and C-to-U RNA editing, which thereby further expand the diversity of their self-antigen repertoire. Interestingly, Aire, the key mediator of mTECs promiscuous gene expression, plays a limited role in the regulation of these transcriptional processes. Conclusions: Our results highlight RNA processing as another layer by which the immune system assures a comprehensive self-representation in the thymus which is required for the establishment of self-tolerance and prevention of autoimmunity. Identification of the number of genes expressed in Aire-KO MEChi Overall design: ~100ng of total RNA was isolated by Trizol extraction from MHC-II high mTECs from a pool of 3 Aire-KO mice. Poly-A-selected transcriptome libraries were generated using the non-directionnal TruSeq V3 RNA Sample Prep Kit (without additional pre-amplification) following the manufacturer''s protocols. Enrichment of DNA fragment with adapter molecules on both ends was done using 15 cycles of PCR amplification using the Illumina PCR mix and primer cocktail. Paired-end (2 × 100 bp) sequencing was performed using the Illumina HiSeq2000 machine.
Extensive RNA editing and splicing increase immune self-representation diversity in medullary thymic epithelial cells.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part, Treatment
View SamplesNK cells are innate immune cells that recognize and kill foreign, virally-infected and tumor cells without the need for prior immunization. NK expansion following viral infection is IL-2 or IL-15-dependent.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part, Treatment
View SamplesNK cells are innate immune cells that recognize and kill foreign, virally-infected and tumor cells without the need for prior immunization. NK expansion following viral infection is IL-2 or IL-15-dependent.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part
View SamplesCD8+T cells are immune cells that recognize foreign antigens on infected and tumor cells, leading to cytokine-dependent expansion and activation of cytotoxicity towards the targets.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part
View SamplesCD8+T cells are immune cells that recognize foreign antigens on infected and tumor cells, leading to cytokine-dependent expansion and activation of cytotoxicity towards the targets.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation.
Sex, Age, Specimen part
View SamplesNK cells are innate immune cells that recognize and kill foreign, virally-infected and tumor cells without the need for prior immunization. NK expansion following viral infection is IL-2 or IL-15-dependent.
Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes.
Sex, Specimen part, Cell line
View SamplesRUNX3 is one of three mammalian Runt-domain transcription factors that regulate gene expression in several types of immune cells. Runx3-deficiency in mice is associated with a multitude of defects in the adaptive and innate immunity systems, including the development of early onset colitis. Our study reveals that conditional deletion of Runx3 specifically in mononuclear phagocytes (MNP) recapitulates the early onset spontaneous colitis seen in Runx3-/- mice. We show that Runx3 is expressed in colonic MNP, including RM and the dendritic cell cDC2 subsets and its loss results in impaired differentiation/maturation of both cell types.
Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes.
Sex, Specimen part
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