SKI-dependent TGFb signaling dictates CD103 expression in CD8+ T cells (ChIP-seq)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA559177 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9920910.fastq.gz | Fastqsanger.gz | |||
| SRR9920911.fastq.gz | Fastqsanger.gz | |||
| SRR9920912.fastq.gz | Fastqsanger.gz | |||
| SRR9920908.fastq.gz | Fastqsanger.gz | |||
| SRR9920909.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 5 |
Similar Datasets
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: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:We report the transcriptome analysis of epidermal CD8 tissue resident memory T (TRM) cells from healthy human skin. Specifically, epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells from healthy human skin were sorted by FACS. Differential gene expression analysis revealed functional dichotomy of epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells.
2017-02-14 | GSE83637 | GEO
Project description:Cytotoxic T cells confer a prognostic benefit in many tumors, including ovarian cancer. We and others have previously identified a subset of CD8+ T cells, namely CD103+CD8+ T cells, that seems to have a better prognostic effect. The aim of this study is to identify how these CD103+ T cells differ from CD103-CD8+ T cells on mRNA level in human samples of ovarian cancer.
2019-03-06 | GSE127888 | GEO
Project description:The Ly6C–CXCR3– naïve CD8 T cells highly express CD103. To understand the biological significance of CD103 expression on naïve CD8 T cells, we performed RNA sequencing on sorted naïve CD8 T cells from WT and CD103-dificient (Itgae–/–) mice to elucidate the function of CD103 expressed on naïve CD8 T cells.
2025-09-24 | GSE295528 | GEO
Project description:The CD8 T cells in the peripheral tissues maintained as a mixture of naïve and memory-phenotype in the steady state, while the mechanism how the balance of naïve and memory-phenotype CD8 T cells is controlled remains unclear. Here, we report that integrin CD103 plays critical role in this process. CD103 is differentially expressed on peripheral CD8 T cells with highest expression on naïve CD8 T cells (Ly6C–CXCR3–) and lowest expression on memory-phenotype CD8 T cells (Ly6C+CXCR3+). To understand the biological significance of CD103 downregulation on memory-phenotype CD8 T cells, we generated transgenic mice that overexpress CD103 under the control of the human CD2 promoter/enhancer so that CD103 is constitutively expressed on all T lineage cells (CD103Tg), and we found that memory-phenotype CD8 T cells are accumulated in CD103Tg mice. Therefore, we performed RNA sequencing on sorted memory-phenotype CD8 T cells from WT and CD103Tg mice to elucidate the molecular mechanism how forced expression of CD103 promotes accumulation of memory-phenotype CD8 T cells.
2025-09-24 | GSE295529 | GEO
Project description:TGFb signaling is a major pathway associated with poor clinical outcome in patients with
advanced metastatic cancers and non-response to immune checkpoint blockade, particularly in the immune-excluded tumor phenotype. While previous pre-clinical studies demonstrated that converting tumors from an excluded to an inflamed phenotype and curative anti-tumor immunity require attenuation of both PD-L1 and TGFb signaling, the underlying cellular mechanisms remain unclear. Recent studies suggest that stem cell-like CD8 T cells (TSCL) can differentiate into non-exhausted CD8 T effector cells that drive durable anti-tumor immunity. Here, we show that TGFb and PD-L1 restrain TSCL expansion as well as replacement of progenitor exhausted and dysfunctional CD8 T cells with non-exhausted IFNghi CD8 T effector cells in the tumor microenvironment (TME). Blockade of TGFb and PD-L1 generated IFNghi CD8 T effector cells with enhanced motility, enabling both their accumulation in the TME and increased interaction with other cell types. Ensuing IFNg signaling markedly transformed myeloid, stromal, and tumor niches to yield a broadly immune-supportive ecosystem. Blocking IFNg completely abolished the effect of anti-PD-L1/ TGFb combination therapy. Our data suggest that TGFb works in concert with PD-L1 to prevent TSCL expansion and replacement of exhausted CD8 T cells with fresh CD8
T effector cells, thereby maintaining the CD8 T cell compartment in a dysfunctional state.
2023-06-16 | MSV000092193 | MassIVE
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:In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs but not CD141+ DCs were able to drive CD103 expression on CD8+ T cells and promote CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound TGF-?1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells. Total RNA were isolated from purified human CD1c+ (BDCA1+) and CD141+ (BDCA3+) mDCs sorted from different tissues, including human blood, spleen and lungs of humanized mice, and human lungs. Eighteen samples in total were analyzed from different donors and tissues.
2013-04-04 | E-GEOD-43184 | biostudies-arrayexpress
Project description:Using mouse model, we show that CD8 tumor-infiltrating T lymphocytes (TIL) include two major resident T cells subpopulations expressing either CD49a or CD103 integrin, with a subset co-expressing CD103 and Tcf-1 transcription factor. Tumor vaccination induces a decrease in the percentage of Tcf-1+CD103+ TRM-like cells and an expansion of CD49a+ TRM displaying an effector/exhausted profile. Tcf-1+CD103+ TRM-cell density increases in tumors from vaccinated transgenic mice constitutively expressing active TGF-beta-type-2-receptor and wild-type mice challenged with neutralizing anti-IL-12 antibodies. Stimulation of mouse and human CD8 T cells with recombinant (r)TGF-beta combined with anti-CD3 antibodies results in increase in the proportion of CD103+ and Tcf-1+CD103+ CD8 T cells, whereas rIL-12 induces decrease in CD103 expression on CD8 T cells.
2025-05-27 | GSE298151 | GEO