Epithelial organoid supports resident memory CD8 T cell differentiation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1047662 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27023807_1.fastq.gz | Fastqsanger.gz | |||
| SRR27023807_2.fastq.gz | Fastqsanger.gz | |||
| SRR27023808_1.fastq.gz | Fastqsanger.gz | |||
| SRR27023808_2.fastq.gz | Fastqsanger.gz | |||
| SRR27023809_1.fastq.gz | Fastqsanger.gz |
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Project description:Epithelial organoid supports resident memory CD8 T cell differentiation [RNA-seq: tcm_spln_cd103_trm_frt]
| PRJNA1129084 | ENA
Project description:Resident Memory T cells (TRM) play a vital role in regional immune defense in barrier organs. Although laboratory rodents have been extensively used to study fundamental TRM biology, issues like poor isolation efficiency, sampling bias and low survival rates have limited our ability to conduct TRM-focused high-throughput assays. Here we engineered a murine vaginal epithelial organoid (VEO)-CD8 T cell coculture system that supports CD8 TRM differentiation in vitro. The three-dimensional VEOs established from adult stem cells resembled stratified squamous vaginal epithelium and induced gradual differentiation of activated CD8 T cells into epithelial TRM. These in vitro generated TRM were phenotypically and transcriptionally similar to in vivo TRM and their epithelial residence phenotype (CD69+ CD103+) was further enhanced with a second cognate-antigen exposure during coculture. TRM differentiation was not affected even when VEOs and CD8 T cells were separated by a semipermeable barrier, indicating soluble factors' involvement. Pharmacological and genetic approaches showed that TGF-β signaling played a crucial role in their differentiation. We found that the VEOs in our model remain susceptible to viral infections and the CD8 T cells were amenable to genetic manipulation; both of which will allow detailed interrogation of antiviral CD8 T cell biology in a reductionist setting. In summary, we established a robust model which captures bonafide TRM differentiation that is scalable, open to iterative sampling, and can be subjected to high throughput assays that will rapidly add to our fundamental understanding of TRM.
2024-07-22 | GSE249204 | GEO
Project description:Resident Memory T cells (TRM) play a vital role in regional immune defense in barrier organs. Although laboratory rodents have been extensively used to study fundamental TRM biology, issues like poor isolation efficiency, sampling bias and low survival rates have limited our ability to conduct TRM-focused high-throughput assays. Here we engineered a murine vaginal epithelial organoid (VEO)-CD8 T cell coculture system that supports CD8 TRM differentiation in vitro. The three-dimensional VEOs established from adult stem cells resembled stratified squamous vaginal epithelium and induced gradual differentiation of activated CD8 T cells into epithelial TRM. These in vitro generated TRM were phenotypically and transcriptionally similar to in vivo TRM and their epithelial residence phenotype (CD69+ CD103+) was further enhanced with a second cognate-antigen exposure during coculture. TRM differentiation was not affected even when VEOs and CD8 T cells were separated by a semipermeable barrier, indicating soluble factors' involvement. Pharmacological and genetic approaches showed that TGF-β signaling played a crucial role in their differentiation. We found that the VEOs in our model remain susceptible to viral infections and the CD8 T cells were amenable to genetic manipulation; both of which will allow detailed interrogation of antiviral CD8 T cell biology in a reductionist setting. In summary, we established a robust model which captures bonafide TRM differentiation that is scalable, open to iterative sampling, and can be subjected to high throughput assays that will rapidly add to our fundamental understanding of TRM.
2024-07-22 | GSE270942 | GEO
Project description:Tissue resident memory T cells (TRM) provide superior protection against infection localised to extra-lymphoid compartments in the body. Here we show that CD103+CD8+ TRM cells develop in skin from killer cell lectin-like receptor (KLR)G1-negative precursors that selectively infiltrate the epithelial layer. In the skin, a combination of chemokine-guided epithelial entry, local interleukin (IL)-15 and transforming growth factor (TGF)-β signalling is required for formation and survival of these long-lived memory cells. Importantly, TRM differentiation results in the gradual acquisition of a unique transcriptional profile that differs from that expressed by memory cells in the circulation and other types of skin-resident intra-epithelial T cells, such as the dendritic epidermal T cells (DETC). We provide a comprehensive molecular and developmental framework for the local differentiation of a distinct type of peripheral memory T cell that contributes to an important first-line of immune defence in barrier tissues such as skin and mucosa. 24 samples were analyzed: 3 replicates of memory gB-T CD8+. CD103+ T cells isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of memory P14 CD8+ T cells isolated from gut of mice on day 60 p.i. with LCMV Armstrong. 3 replicates of memory gB-T CD8+ T cells from the lung of mice on day 30 p.i. with influenza WSN. 3 replicates of memory CD62L high CD8+ T cells from the spleen of mice on day 30 p.i. with HSV KOS. 3 replicates of memory CD62L low CD8+ T cells from the spleen of mice of day 30 p.i. with HSV KOS. 3 replicates of γδ-DETC isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of αβ-DETC from naive TCRδ-/- mice; and 3 replicates of naive gB-T CD8+ T cells from the spleen of naive gB-T transgenic mice.
2013-10-01 | E-GEOD-47045 | biostudies-arrayexpress
Project description:CD8 Tissue Resident Memory (TRM) induction
| PRJNA1036221 | ENA
Project description:Resident Memory T cells (TRM) play a vital role in regional immune defense in barrier organs. Although laboratory rodents have been extensively used to study fundamental TRM biology, poor isolation efficiency, sampling bias and low cell survival rates have limited our ability to conduct TRM-focused high-throughput assays. Here, we engineered a murine vaginal epithelial organoid (VEO)-CD8 T cell co-culture system that supports CD8 TRM differentiation in vitro. The three-dimensional VEOs established from murine adult stem cells resembled stratified squamous vaginal epithelium and induced gradual differentiation of activated CD8 T cells into epithelial TRM. These in vitro generated TRM were phenotypically and transcriptionally similar to in vivo TRM, and key tissue residency features were reinforced with a second cognate-antigen exposure during co-culture. TRM differentiation was not affected even when VEOs and CD8 T cells were separated by a semipermeable barrier, indicating soluble factors' involvement. Pharmacological and genetic approaches showed that TGF-β signaling played a crucial role in their differentiation. We found that the VEOs in our model remained susceptible to viral infections and the CD8 T cells were amenable to genetic manipulation; both of which will allow detailed interrogation of antiviral CD8 T cell biology in a reductionist setting. In summary, we established a robust model which captures bonafide TRM differentiation that is scalable, open to iterative sampling, and can be subjected to high throughput assays that will rapidly add to our understanding of TRM.
| S-EPMC10705482 | biostudies-literature
Project description:Tissue resident memory (Trm) represent a newly described memory T cell population. We have previously characterized a population of Trm that persists within the brain following acute virus infection. Although capable of providing marked protection against a subsequent local challenge, brain Trm do not undergo recall expansion following dissociation from the tissue. Furthermore, these Trm do not depend on the same survival factors as the circulating memory T cell pool as assessed either in vivo or in vitro. To gain greater insight into this population of cells we compared the gene-expression profiles of Trm isolated from the brain to circulating memory T cells isolated from the spleen following an acute virus infection. Trm displayed altered expression of genes involved in chemotaxis, expressed a distinct set of transcription factors and overexpressed several inhibitory receptors. Cumulatively, these data indicates that Trm are a distinct memory T cell population disconnected from the circulating memory T cell pool and displaying a unique molecular signature which likely results in optimal survival and function within their local environment. 13 samples were analyzed: 5 replicates of memory OT-I CD8+.CD103- T cells isolated from the spleen of mice on day 20 p.i. with VSV-OVA. 5 replicates of memory OT-I CD8+CD103+ T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA; and 3 replicates of memory OT-I.CD8+ CD103- T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA
2012-08-29 | E-GEOD-39152 | biostudies-arrayexpress
Project description:A specialized population of memory CD8+ T-cells resides in the epithelium of the respiratory tract to maintain protection against recurring infections. These cells express CD69 and the integrin αβ7 (CD103) and correspond to tissue resident memory T-cells (TRM) also described in intestine, liver and brain. A less well characterized population of CD103- CD8+ T-cells also resides in lungs and expresses markers characteristic of effector memory T-cells (TEM). We determined the transcriptional profiles of these memory CD8+ T-cell subsets retrieved from human lung resection samples and compared these with corresponding T-cell populations from peripheral blood of the same individuals. Our results demonstrate that each of the populations exhibits a distinct transcriptional identity. We found that the lung environment has a major impact on gene expression profiles. Thus, transcriptomes from CD103+ and CD103- subsets from lungs are much more resemblant to one another than to those from CD103+ or CD103- memory CD8+ T-cells from blood. TRM express specific sets of chemokine receptors, in accordance with their unique migratory properties. Furthermore, these cells constitutively express cytokine and cytotoxic genes for immediate effector function and chemokines to attract auxiliary immune cells. At the same time, multiple genes encoding inhibitory regulators are also expressed. This suggests that rapid ability to unleash effector functions is counterbalanced by programmed restraint, a combination that may be critical in the exposed but delicate tissue of the lung. Comprehensive sets of transcription factors were identified that characterize the memory CD8+ populations in the lungs. Prominent among these were components of the Notch pathway. Using mice genetically lacking expression of the NOTCH1 and NOTCH2 receptors in T-cells, we demonstrated that Notch controls both the number of lung TRM as well as the function of lung TEM. Our data illustrate the adaptation of lung resident T-cells to the requirements of the respiratory epithelial environment. Defining the molecular imprinting of these cells is important for rational vaccine design and may help to improve the properties of T-cells for adoptive cellular therapy. Material was collected from a total of 6 subjects. Three patients underwent a lobectomy for a peripheral primary lung tumor and three received lung transplantation because of end-stage pulmonary disease (COPD). Lung mononuclear cells where isolated after digestion of the partial or complete human lung resection material. Paired peripheral blood mononuclear cells were also isolated. CD8+CD16-CD56- T-cells were sorted for expression of CD103 (ITGAE). Lung and blood derived CD103+ and CD103- T-cell fractions were directly lysed after FACS sorting or stimulated overnight with antiCD3/28 beads. Due to the low frequency of resting (non-stimulated) CD103+ T-cells in peripheral blood this subset was obtained from five non-related buffy coat donors. RNA was isolated from 36 sorted cell samples and hybridized on Illumina HumanHT-12 V4.0 microarrays. Eight microarray samples (including two samples from the buffy coat donors) were excluded after hybridization since their average signal was too low.
2016-10-23 | E-GEOD-61397 | biostudies-arrayexpress
Project description:TGF-beta signaling is required for the differentiation of gut-resident memory CD8 T cells. Here, we showed that the deficiency of transcription factor T-bet partially rescued the differentiation of TGF-beta receptor deficient gut-resident memory CD8 T cells.
2021-10-06 | GSE184628 | GEO
Project description:TGF-beta signaling is required for the differentiation of gut-resident memory CD8 T cells. Here, we showed that the deficiency of transcription factor T-bet partially rescued the differentiation of TGF-beta receptor deficient gut-resident memory CD8 T cells.
2021-10-06 | GSE184627 | GEO