RNA-seq analysis of cRel+/+ and cRel-/- Tregs
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE154166 | GEO | 2021/05/29
REPOSITORIES: GEO
Similar Datasets
Project description:RNA-seq analysis of cRel+/+ and cRel-/- Tregs
| PRJNA645308 | ENA
Project description:Using Foxp3.RFP Rag.GFP reporter mice, mature Tregs in the thymus were characterized by performing RNA sequencing on Rag.GFP– and Rag.GFP+ Tregs that were isolated from the thymus and Tregs isolated from the spleen
2020-07-27 | GSE153154 | GEO
Project description:The mechanism of egress of mature regulatory T cells (Tregs) from the thymus to the periphery remains enigmatic, as does the nature of those factors expressed in the thymic environment. Here, we examined the fate of thymic Tregs in TNFα/RelA double-knockout (TA-KO) mice, because TA-KO mice retain a Treg population in the thymus but have only a small Treg population at the periphery. Transplantation of whole TA-KO thymus to under the kidney capsule of Rag1 null mice failed to induce the production of donor-derived splenic Tregs expressing neuropilin-1 (Nrp1), which was reported to be a marker of naturally occurring Tregs, indicating that TA-KO thymic Tregs either do not leave the thymus or are lost at the periphery. We next transplanted enriched TA-KO thymic Tregs to the peripheries of TA-KO mice and traced mouse survival. Transplantation of TA-KO thymic Tregs rescued the lethality in TA-KO mice, demonstrating that TA-KO thymic Tregs remain functional at the periphery. The TA-KO thymic Treg population had highly demethylated CpG motifs in the foxp3 locus, indicating that the cells were arrested at a late-mature stage. Also, the population included a large subpopulation of Tregs expressing IL-7Rα, which is a possible marker of late-mature Tregs. Finally, TA-KO fetal liver chimeric mice developed an Nrp1+ splenic Treg population from TA-KO cells, suggesting that Treg arrest is caused by a lack of RelA in the thymic environment. Together, these results suggest that egress of mature Tregs from the thymus depends on RelA in the thymic environment. For the isolation of thymic Tregs, CD4+CD8α-CD25hi thymocytes were isolated from five 1.5- to 2-week-old TNFα-KO or TA-KO mice by using a FACSAria cell sorter. For the isolation of thymic stromal cells, 10 thymi from 1.5- to 2-week-old TNFα-KO or TA-KO mice were minced with scissors and treated with RPMI 1640 supplemented with 2% FCS, 0.2 mg/ml collagenase (Roche, Basel, Switzerland), 0.2 mg/ml dispase I (Roche), and 100 U/ml DNase I (Life Technologies) for 30 min with stirring. Digested thymi were centrifuged in a Percoll (GE Healthcare Bio-Sciences, Piscataway, NJ, USA) gradient (density, 1.115, 1.065, and PBS) at 1400g for 30 min. Cells in the upper layer were collected, and the CD45-EpCAM+ (thymic epithelial cells) and CD45+EpCAM- populations (enriched thymic stromal cells containing macrophages or dendritic cells) were sorted.
2015-03-04 | E-GEOD-64191 | biostudies-arrayexpress
Project description:The mechanism of egress of mature regulatory T cells (Tregs) from the thymus to the periphery remains enigmatic, as does the nature of those factors expressed in the thymic environment. Here, we examined the fate of thymic Tregs in TNFα/RelA double-knockout (TA-KO) mice, because TA-KO mice retain a Treg population in the thymus but have only a small Treg population at the periphery. Transplantation of whole TA-KO thymus to under the kidney capsule of Rag1 null mice failed to induce the production of donor-derived splenic Tregs expressing neuropilin-1 (Nrp1), which was reported to be a marker of naturally occurring Tregs, indicating that TA-KO thymic Tregs either do not leave the thymus or are lost at the periphery. We next transplanted enriched TA-KO thymic Tregs to the peripheries of TA-KO mice and traced mouse survival. Transplantation of TA-KO thymic Tregs rescued the lethality in TA-KO mice, demonstrating that TA-KO thymic Tregs remain functional at the periphery. The TA-KO thymic Treg population had highly demethylated CpG motifs in the foxp3 locus, indicating that the cells were arrested at a late-mature stage. Also, the population included a large subpopulation of Tregs expressing IL-7Rα, which is a possible marker of late-mature Tregs. Finally, TA-KO fetal liver chimeric mice developed an Nrp1+ splenic Treg population from TA-KO cells, suggesting that Treg arrest is caused by a lack of RelA in the thymic environment. Together, these results suggest that egress of mature Tregs from the thymus depends on RelA in the thymic environment.
2015-03-04 | GSE64191 | GEO
Project description:Characterization of mature Tregs in the thymus
| PRJNA641641 | ENA
Project description:Tregs from spleen and thymus of naive Wild-type mice and mice lacking Dendritic Cells (deltaDC) were analyzed. Thymus derived Tregs of both strains show similar expression patterns, peripheral splenic Tregs from deltaDC mice differ from Tregs of WT mice.
2019-09-27 | GSE120690 | GEO
Project description:NF-kB is a transcriptional factor that consists in homo and heterodimers of the large family of Rel subunits. Among the most important functions for NF-kB, initiation of immunological/inflammatory responses and regulation of cell proliferation/apoptosis which are the major features of severe infections. Although the role of NF-kB is crucial in host defense against pathogens, mice deficient for individual subunits of NF-kB have not been explored in murine models of polymicrobial infection. In this report, we have investigated in vivo the consequences of cRel subunit deficiency in the survival to polymicrobial infection. We have also approached the underlying mechanisms of the host defense by analyzing cytokine production, bacterial clearance and the distribution of innate and adaptive immune cells. Absence of cRel enhances mice mortality to polymicrobial sepsis. The decreased survival of cRel-/- animals upon infection is not related to altered local mechanisms of innate defense such as the peritoneal recruitment of the Gr.1+CD11b+ phagocytic cells and the bacterial clearance. However, cRel deficiency allows to altered systemic cytokine response associated to sustained loss of the lymphoïd subset CD8a+ of spleen dendritic cells, key antigen-presenting cells for the initiation of the adaptive immunity. Genome-wide analysis of the systemic host response to polymicrobial sepsis reveals inflammatory/immune and apoptotic gene signatures associated to cRel subunit. In this study we identified the NF-kB member cRel, as a key factor which plays a critical role in survival to polymicrobial sepsis and also as a regulatory transcription subunit controlling the inflammatory and the adaptive immune responses in severe infection.
2011-10-14 | E-MEXP-2944 | biostudies-arrayexpress
Project description:IL18 signaling promotes homing of mature Tregs into the thymus
| PRJNA641635 | ENA
Project description:Characterization of mature IL18R- and IL18R+ Tregs in the thymus
| PRJNA641639 | ENA
Project description:In this study we performed RNA sequencing to determine and compare the transcriptome of regulatory T cells (Tregs) present in the thymus, placenta, spleen and white adipose tissue (FAT) of pregnant mice. We further assessed how the expression of the receptor Rank in the thymic medullary epithelia affects the transcriptional program of these Treg populations. For the isolation of viable and bona fide Tregs, we first generated RankWt (wild type control mice) and RankΔFoxn1 (which lack expression of Rank in the thymic epithelia) and further crossed them to mice that express GFP from the Foxp3 promoter. Neuropilin1 was used to mark the thymic origin of the Tregs. Equal numbers of Tregs (280 cells) were sorted as CD45-CD8-CD4+GFP+Neuropilin1High cells from the thymus and placenta of RankWtFoxp3GFP/GFP and RankΔFoxn1Foxp3GFP/GFP pregnant females at E17.5 (both samples from the same female; n=4 females per genotype). Thymus Tregs from non-pregnant littermate female mice for each genotype cohort were also studied. To increase robustness, the 280 placental Tregs were purified from 5 individual placentas per pregnant female (56 Tregs/placenta). Our study is the first one to determine the transcriptome of thymus and placenta Tregs during pregnancy and reveals that, partially dependent on Rank expression in the thymic epithelia, placental-resident Tregs are molecularly distinct from thymic Tregs. In a separate experiment with different pregnant mice than those used for thymus and placenta analysis, VAT Tregs (20-30 cells) and splenic Tregs (150 cells) were sorted (both samples from the same female) by using the same mouse lines (Rank Wt and RankΔFoxn1), embryological days of analysis (E17.5) and sorting strategies.
2020-10-21 | GSE97666 | GEO