Effect of Aire deficiency on peripheral Tgd17 gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE89258 | GEO | 2016/10/28
SECONDARY ACCESSION(S): PRJNA350846
REPOSITORIES: GEO
Similar Datasets
Project description:Aire is an important transcription regulator that mediates a role in central tolerance via promoting the promiscuous expression of tissue-specific antigens in the thymus. Although several mouse models of Aire-deficiency have been described, none has analysed the phenotype induced by a mutation that emulates the common 13bp deletion in human APECED by disrupting the first PHD domain in exon 8. Aire-deficient mice with a corresponding mutation showed some disturbance of the medullary epithelial compartment, but at the phenotypic level their T cell compartment appeared relatively normal in the thymus and periphery. An increase in the number of activated T cells was evident, and autoantibodies against several organs were detected. At the histological level, lymphocytic infiltration of several organs indicated the development of autoimmunity, though symptoms were mild and quality of life for Aire-deficient mice appeared equivalent to wild-type littermates, with the exception of male infertility. Vbeta and CDR3 length analysis suggested that each Aire-deficient mouse developed it own polyclonal autoimmune repertoire. Finally, given the prevalence of candidiasis in APECED patients, we examined the control of infection with Candida albicans in Aire-deficient mice. No increase in disease susceptibility was found for either oral or systematic infection. These observations support the view that additional genetic and/or environmental factors contribute substantially to the overt nature of autoimmunity associated with Aire mutations, even for mutations identical to those found in humans with APECED. Keywords: Gene expression comparison between genotypes In this experiment there are 5 samples altogether which consist of two biological replicates of Aire knock-out mTECs and 3 biological replicates of wild type mTECs.
2009-03-15 | E-GEOD-14365 | biostudies-arrayexpress
Project description:Aire is an important transcription regulator that mediates a role in central tolerance via promoting the promiscuous expression of tissue-specific antigens in the thymus. Although several mouse models of Aire-deficiency have been described, none has analysed the phenotype induced by a mutation that emulates the common 13bp deletion in human APECED by disrupting the first PHD domain in exon 8. Aire-deficient mice with a corresponding mutation showed some disturbance of the medullary epithelial compartment, but at the phenotypic level their T cell compartment appeared relatively normal in the thymus and periphery. An increase in the number of activated T cells was evident, and autoantibodies against several organs were detected. At the histological level, lymphocytic infiltration of several organs indicated the development of autoimmunity, though symptoms were mild and quality of life for Aire-deficient mice appeared equivalent to wild-type littermates, with the exception of male infertility. Vbeta and CDR3 length analysis suggested that each Aire-deficient mouse developed it own polyclonal autoimmune repertoire. Finally, given the prevalence of candidiasis in APECED patients, we examined the control of infection with Candida albicans in Aire-deficient mice. No increase in disease susceptibility was found for either oral or systematic infection. These observations support the view that additional genetic and/or environmental factors contribute substantially to the overt nature of autoimmunity associated with Aire mutations, even for mutations identical to those found in humans with APECED. Keywords: Gene expression comparison between genotypes
2009-03-15 | GSE14365 | GEO
Project description:RNA-sequencing of Aire-ILC3 cells from wild-type and Aire-deficient mice
| PRJEB27961 | ENA
Project description:Mutations in the gene encoding the transcription factor AutoImmune REgulator (AIRE) are responsible for the ‘Autoimmune PolyEndocrinopathy Candidiasis Ecodermal Dystrophy’ syndrome. AIRE directs expression of tissue restricted antigens in the thymic medulla and in lymph node stromal cells and thereby substantially contributes to induction of immunological tolerance to self-antigens. Data from experimental mouse models showed that AIRE-deficiency leads to impaired deletion of autospecific T cell precursors. However, a potential role for AIRE in the function of regulatory T cell populations, which are known to play a central role in prevention of immunopathology, has remained elusive. Regulatory T cells of CD8+CD28low phenotype efficiently control immune responses in experimental autoimmune and colitis models in mice. We here show that CD8+CD28low Treg from AIRE-deficient mice are transcriptionally and phenotypically normal, exert efficient suppression of in vitro immune responses, but completely fail to prevent experimental colitis in vivo. Our data therefore demonstrate that AIRE plays an important role in the in vivo function of a naturally occurring regulatory T cell population. Total RNA was extracted from CD8+CD28low regulatory T lymphocytes isolated from wildtype and Aire-deficient C57BL/6 mice for comparison of gene expression profiles.
2011-06-22 | E-GEOD-30129 | biostudies-arrayexpress
Project description:Bulk RNA-seq analysis of mouse dendritic cells (DCs) in Aire-reporter strain (AGF-KI: human AIRE and GFP-Flag tag knock-in). Aire+ DCs and Aire- DCs were isolated from lymph nodes and bone marrow, using Aire-sufficient (+/KI) and Aire-deficient background (-/KI).
2023-01-05 | GSE211006 | GEO
Project description:We used freshly isolated lacrimal glands isolated from wild type and Aire-/- mice on a Balbc background. Mice were 5 weeks of age, with an n=4 for wild type and n=3 for Aire-deficient.
2019-05-14 | GSE131073 | GEO
Project description:The deficiency of Aire, a transcriptional regulator whose defect results in the development of autoimmunity, is associated with reduced expression of tissue-restricted self-Ags (TRAs) in medullary thymic epithelial cells (mTECs). Although the mechanisms underlying Aire-dependent expression of TRAs need to be explored, the physical identification of the target(s) of Aire has been hampered by the low and promiscuous expression of TRAs. We have tackled this issue by engineering mice with augmented Aire expression. Integration of the transcriptomic data from Aire-augmented and Aire-deficient mTECs revealed that a large proportion of so-called Aire-dependent genes, including those of TRAs, may not be direct transcriptional targets downstream of Aire. Rather, Aire induces TRA expression indirectly through controlling the heterogeneity of mTECs, as revealed by single-cell analyses. In contrast, Ccl25 emerged as a canonical target of Aire, and we verified this both in vitro and in vivo. Our approach has illuminated the Aire?s primary targets while distinguishing them from the secondary targets.
2021-10-13 | GSE155331 | GEO
Project description:Autoimmune regulator (AIRE) is a transcriptional regulator. We here assess the role for AIRE in primary human neutrophils. We found that the functional role for AIRE in neutrophils is to regulate the extrinsic apoptotic pathway involving the Fas/TNFR death receptors and Cathepsin G and the expression of unique immune mediators.
2024-01-25 | PXD047989 | Pride
Project description:We explored the role of the autoimmune regulator (Aire) gene in supporting fetal tolerance during pregnancy with transgenic diphtheria toxin receptor (Aire-DTR) mice, in which Aire-expressing populations can be deleted by injection of diptheria toxins (DT). Aire-expressing cell depletion was found to cause intruterine growth restriction (IUGR) in both allogenic and syngeneic pregnancies. This phenotype is immune-mediated, as IUGR is rescued in Rag1-deficient mice, and involves a memory response, as demonstrated by severe IUGR in second pregnancies. We further explored this phenotype through single-cell RNA sequencing of leukocytes obtained from the secondary lymphoid organs (uterine and non-uterine-draining lymph nodes) of wild-type (WT) and Aire-DTR pregnant dams during allogeneic pregnancy. Transciptomic data reveals a shift in population distributions from naïve to effector CD4+ and CD8+ T cells in Aire-DTR mice. Within the effector CD4+ compartment, there was a significant shift away from Tregs and toward mature T effectors, most notably T follicular helper (Tfh) and Th17 cells. These findings support the idea that Aire is essential in maintaining immune homeostasis.
2021-05-18 | GSE174521 | GEO
Project description:The goal of the study was to sequence mRNA expression from sorted medullary thymic epithelial cell (mTEC) subsets in inducible Aire-CreERT2.R26-Stopfl-tdTomato lineage tracing mice after a pulse chase. Four cell subsets were sorted 7 days after a single 2mg pulse of tamoxifen administered by oral gavage. 4 biological replicates (1,2,3,4) were collected derived from 12 pooled thymi per replicate. From the DAPI-;CD45-;EpCAM+ TEC pool, cells were sorted as: pre-Aire (MHCIIlo;RFP-), early-Aire (MHCIIhi;RFP-), late-Aire (MHCIIhi;RFP+), and post-Aire (MHCIIlo;RFP+). The data were used to identify differentially expressed genes across the four mTEC subsets to examine mTEC heterogeneity and identify novel mTEC subpopulations.
2018-05-19 | GSE114651 | GEO