Improving Thymus Implantation for Congenital Athymia with Interleukin-7
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1033646 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26590577_1.fastq.gz | Fastqsanger.gz | |||
| SRR26590577_2.fastq.gz | Fastqsanger.gz | |||
| SRR26590578_1.fastq.gz | Fastqsanger.gz | |||
| SRR26590578_2.fastq.gz | Fastqsanger.gz | |||
| SRR26590579_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Patients receiving thymus implantation develop a functional but incomplete T cell compartment. Our objective was to develop a mouse model to study clinical thymus implantation in congenital athymia and to optimize implantation procedures to maximize T cell education and expansion of naïve T cells. Treating implanted mice with recombinant interleukin (IL-7) promoted homeostatic expansion that improved T cell development, expanded the T cell receptor repertoire, and normalized the naïve T cell compartment.
2023-11-29 | GSE246565 | GEO
Project description:ObjectivesThymus implantation is a recently FDA-approved therapy for congenital athymia. Patients receiving thymus implantation develop a functional but incomplete T cell compartment. Our objective was to develop a mouse model to study clinical thymus implantation in congenital athymia and to optimise implantation procedures to maximise T cell education and expansion of naïve T cells.MethodsUsing Foxn1 nu athymic mice as recipients, we tested MHC-matched and -mismatched donor thymi that were implanted as fresh tissue or cultured to remove donor T cells. We first implanted thymus under the kidney capsule and then optimised intramuscular implantation. Using competitive adoptive transfer assays, we investigated whether the failure of newly developed T cells to expand into a complete T cell compartment was because of intrinsic deficits or whether there were deficits in engaging MHC molecules in the periphery. Finally, we tested whether recombinant IL-7 would promote the expansion of host naïve T cells educated by the implanted thymus.ResultsWe determined that thymus implants in Foxn1 nu athymic mice mimic many aspects of clinical thymus implants in patients with congenital athymia. When we implanted cultured, MHC-mismatched donor thymus into Foxn1 nu athymic mice, mice developed a limited T cell compartment with notably underdeveloped naïve populations and overrepresented memory-like T cells. Newly generated T cells were predominantly educated by MHC molecules expressed by the donor thymus, thus potentially undergoing another round of selection once in the peripheral circulation. Using competitive adoptive transfer assays, we compared expansion rates of T cells educated on donor thymus versus T cells educated during typical thymopoiesis in MHC-matched and -mismatched environments. Once in the circulation, regardless of the MHC haplotypes, T cells educated on a donor thymus underwent abnormal expansion with initially more robust proliferation coupled with greater cell death, resembling IL-7 independent spontaneous expansion. Treating implanted mice with recombinant interleukin (IL-7) promoted homeostatic expansion that improved T cell development, expanded the T cell receptor repertoire, and normalised the naïve T cell compartment.ConclusionWe conclude that implanting cultured thymus into the muscle of Foxn1 nu athymic mice is an appropriate system to study thymus implantation for congenital athymia and immunodeficiencies. T cells are educated by the donor thymus, yet naïve T cells have deficits in expansion. IL-7 greatly improves T cell development after thymus implantation and may offer a novel strategy to improve outcomes of clinical thymus implantation.
| S-EPMC10665642 | biostudies-literature
Project description:Thymus is the important immune organ, responsible for T cell development and differentiation.We conduct rhesus monkey thymus proteomics of FNC.
2024-08-10 | PXD050624 | Pride
Project description:Extracellular vesicles (EVs) are important mediators of embryo attachment and outgrowth critical for successful implantation. While EVs have garnered immense interest in their therapeutic potential in assisted reproductive technology by improving implantation success, their large-scale generation remains a major challenge. Here, we report a rapid and scalable production of nanovesicles (NVs) from human trophectoderm cells (hTSCs) via membrane extrusion; these NVs can be generated in approximately 6 hours with a 20-fold higher yield than EVs isolated from the same number of cells. NVs display similar biophysical traits (morphologically intact, spherical, 90-130 nm) to EVs, and are laden with hallmark players of implantation (ITGA2/V, ITGB1, PRDX1, SOD2, and MFGE8) that include cell-matrix adhesion and extracellular matrix organisation proteins. Functionally, NVs are readily taken up by low-receptive endometrial HEC1A cells and reprogram their proteome towards a receptive phenotype that support hTSC spheroid attachment. Moreover, a single dose treatment of NVs significantly enhanced adhesion and spreading of mouse embryo trophoblast on fibronectin matrix. We show functional potential of NVs in enhancing embryo implantation and highlight their rapid and scalable generation, amenable to clinical utility.
2023-02-20 | PXD038856 | Pride
Project description:Thymus is the important immune organ, responsible for T cell development and differentiation.We conduct rat thymus proteomics study of FNC.
2024-08-10 | PXD050620 | Pride
Project description:Anaylsis differentially expressed genes of mouse peri-implanted uteri comparing pre-implantation uteri (Day2, Day3 and Day4) with post-implantation uteri (Day6, Day7 and Day8) by microassay. This study has built a meaningful basis for future investigation in elucidating the molecular nature of maternal-fetal interactions during pregnancy establishment and maintenance. Pre-implantation uteri VS. Post-implantation uteri. Three biological replicates of each experiments: pre-implantation uteri (Day2, Day3 and Day4): 234, 234①, 234②; 3 mixture of post-implantation uteri (Day6, Day7 and Day8): 678, 678①, 678②. Two hybridizations were performed by using a reverse fluorescence strategy (Cy3, Cy5) for each sample.
2011-06-30 | E-GEOD-26615 | biostudies-arrayexpress