RNA-seq transcriptome analysis of epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- T cells from healthy human skin
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE83637 | GEO | 2017/02/14
SECONDARY ACCESSION(S): PRJNA326541
REPOSITORIES: GEO
Similar Datasets
Project description:CD49a marks highly cytotoxic epidermal tissue-resident memory (TRM)-cells, but their molecular circuitry and relationships to circulating populations are poorly defined. We demonstrate enrichment of RUNX family transcription factor binding motifs in human epidermal CD8+CD103+CD49a+ TRM-cells, paralleled by high RUNX2 and RUNX3 protein expression. Clonal overlap between epidermal CD8+CD103+CD49a+ TRM-cells and circulating memory CD8+CD45RA–CD62L+ T-cells identified a reservoir of circulating cells with potential to seed cytotoxic TRM-cells in new sites. Upon IL-15 and TGF-β stimulation, subsets of circulating CD8+CD45RA–CD62L+ T-cells acquired CD49a expression and cytotoxic transcriptional profiles in a RUNX2 and RUNX3 dependent manner. In contrast, knock-out of RUNX3, but not RUNX2, prevented CD103 expression. In melanoma, high RUNX2, but not RUNX3, transcription correlated with a cytotoxic CD8+CD103+CD49a+ TRM cell signature and overall patient survival. Together, our results indicate that combined RUNX2 and RUNX3 activity promotes the differentiation of cytotoxic CD8+CD103+CD49a+ TRM-cells, providing immunosurveillance of infected and malignant cells.
2024-04-30 | GSE232238 | GEO
Project description:CD49a marks highly cytotoxic epidermal tissue-resident memory (TRM)-cells, but their molecular circuitry and relationships to circulating populations are poorly defined. We demonstrate enrichment of RUNX family transcription factor binding motifs in human epidermal CD8+CD103+CD49a+ TRM-cells, paralleled by high RUNX2 and RUNX3 protein expression. Clonal overlap between epidermal CD8+CD103+CD49a+ TRM-cells and circulating memory CD8+CD45RA–CD62L+ T-cells identified a reservoir of circulating cells with potential to seed cytotoxic TRM-cells in new sites. Upon IL-15 and TGF-β stimulation, subsets of circulating CD8+CD45RA–CD62L+ T-cells acquired CD49a expression and cytotoxic transcriptional profiles in a RUNX2 and RUNX3 dependent manner. In contrast, knock-out of RUNX3, but not RUNX2, prevented CD103 expression. In melanoma, high RUNX2, but not RUNX3, transcription correlated with a cytotoxic CD8+CD103+CD49a+ TRM cell signature and overall patient survival. Together, our results indicate that combined RUNX2 and RUNX3 activity promotes the differentiation of cytotoxic CD8+CD103+CD49a+ TRM-cells, providing immunosurveillance of infected and malignant cells.
2024-04-30 | GSE232236 | 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: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.
2013-10-01 | GSE47045 | GEO
Project description:Current cancer immunotherapies promote recovery of CD103+ tissue-resident memory T cells (Trm) population of the tumor-infiltrating T lymphocytes (TILs). However, not all treated patients exhibit improved anti-tumor immunity and survival, likely due to the immunophenotypical diversity among the CD103+ Trm TILs. Utilising multifaceted proteomics approaches and patients’ clinical analyses, we discovered an unusual subset of CD8+ Trm TILs expressing non-canonical integrin β3 early during T cells activation. The integrin β3 surprisingly heterodimerises with CD103 on T cells, leading to unconventional granulysin-mediated cytotoxicity, elevated alternative bioenergy usage and efficient T cell migration, with minimal overall exhaustion. Importantly, early-stage non-small cell lung carcinoma (NSCLC) patients with enriched presence of integrin β3+CD103+ Trm TILs exhibited better clinical prognosis, with improved T cell immunophenotype, hence confirming the beneficial role of this unusual subset of Trm TILs. These unconventional anti-tumor T cell features provide new avenues and future opportunities for designing better translational immunotherapy strategies.
2024-02-14 | PXD031794 | Pride
Project description:CD8 tissue-resident memory T (TRM) cells provide front-line protection at barrier tissues; however, mechanisms regulating TRM cell development are not completely understood. Priming dictates the migration of effector T cells to the tissue, while factors in the tissue induce in situ TRM cell differentiation. Whether priming also regulates in situ TRM cell differentiation uncoupled from migration is unclear. Here, we demonstrate that T cell priming in the mesenteric lymph nodes (MLN) regulates CD103+ TRM cell differentiation in the intestine. In contrast, T cells primed in the spleen were impaired in the ability to differentiate into CD103+ TRM cells after entry into the intestine. MLN priming initiated a CD103+ TRM cell gene signature and licensed rapid CD103+ TRM cell differentiation in response to factors in the intestine. Licensing was regulated by retinoic acid signaling and primarily driven by factors other than CCR9 expression and CCR9-mediated gut homing. Thus, the MLN is specialized to promote intestinal CD103+ CD8 TRM cell development by licensing in situ differentiation.
2023-02-13 | GSE223983 | GEO
Project description:RNA-seq transcriptome analysis of epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- T cells from healthy human skin
| PRJNA326541 | ENA
Project description:Initially identified as a functional marker for resident-memory (Trm) CD8+ T cells, CD103 (encoded by ITGAE gene) has broad roles in immunity and diseases. Elucidating the function and regulation of CD103 is thus of importance. This study revealed that the CD103 expression by CD8 T cells under steady state contributes to the clearance of acute viral infection. More importantly, it discovered TGF-SKI-Smad4 a critical signaling axis in restricting CD103 expression in CD8+ T cells for their function. Mechanistically, by ChIP-Seq and ChIP analysis, SKI associated with Smad4 was found to directly and epigenetically suppress CD103 transcription. This study therefore reveals a novel TGF-SKI-Smad4 pathway to specifically enable CD103 expression in CD8+ T cells for protective immunity.
2020-07-28 | GSE135533 | GEO
Project description:We report the RNA sequencing of both non-restimulated and restimulated (using anti CD3/CD28 cross-linking) antigen-experienced (CD44+) mouse lung CD8 T cells 21 days post X31 influenza A infection subsetted by integrin expression of CD49a and CD103. After restimulation, all four subsets (CD49a+CD103+, CD49a+CD103-,CD49a-CD103+, CD49a-CD103-) demonstrate global differences and separate in principle component analysis space, with CD49a+ groups showing elevated transcripts for a number of effector functions. The non-restimulated T cells separate out into CD49a+CD103+/- and CD49a-CD103+/- groups. CD49a serves as a correlate of effector transcripts in mouse lungs to a greater degree than CD103 in both non-restimulated and restimulated conditions.
2021-07-30 | GSE179653 | GEO
Project description:Tissue-resident memory T cells (TRM) persist locally in non-lymphoid tissues where they provide front-line defense against recurring insults. TRM at barrier surfaces express the markers CD103 and/or CD69 which function to retain them in epithelial tissues. In humans, neither the long-term migratory behavior of TRM nor their ability to re-enter the circulation and potentially migrate to distant tissue sites have been investigated. Using tissue explant cultures, we found that CD4+CD69+CD103+ TRM in human skin can downregulate CD69 and exit the tissue. Additionally, we identified a skin-tropic CD4+CD69-CD103+ population in human lymph and blood that is transcriptionally, functionally and clonally related to the CD4+CD69+CD103+ TRM population in the skin. Using a skin xenograft model, we confirmed that a fraction of the human cutaneous CD4+CD103+ TRM population can re-enter circulation, and migrate to secondary human skin sites where they re-assume a TRM phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4+ T cell memory in humans.
2019-05-25 | GSE131770 | GEO