Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1102726 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28753200_1.fastq.gz | Fastqsanger.gz | |||
| SRR28753200_2.fastq.gz | Fastqsanger.gz | |||
| SRR28753197_1.fastq.gz | Fastqsanger.gz | |||
| SRR28753197_2.fastq.gz | Fastqsanger.gz | |||
| SRR28753198_1.fastq.gz | Fastqsanger.gz |
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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:Following an infection, CD4+ lymphocytes can differentiate into long-lived memory T cells, some of which circulate through the secondary lymphoid organs (SLOs) while a population lodges in non-lymphoid tissues. While CD4+ T cells in SLOs have been examined, the developmental origins and transcriptional regulation of tissue-resident memory T cells (TRM) remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profile of virus-specific CD4+ TRM in the small intestine (SI) following acute lymphocytic choriomeningitis virus (LCMV) infection. LCMV-specific CD4+ TRM at day 7 of infection shared a gene-expression program and chromatin profile with TH1 cells and progressively acquired a mature TRM program by day 21 memory time point, supporting a developmental relationship between TRM and TH1 subsets. Furthermore, we demonstrated that TRM cells expressed genes associated with both effector and memory T cell fates, including the transcriptional regulators Blimp1, Id2, and Bcl6 which were necessary for CD4+ TRM differentiation. TH1-associated Blimp1 and Id2 were both required for early TRM formation, while TFH-associated Bcl6 initially inhibited TRM differentiation but was critical for development of long-lived TRM cells. Our results identify new significance for TFs previously associated with circulating CD4+ T cell populations and their roles in driving SI CD4+ TRM differentiation.
2023-06-30 | GSE184260 | GEO
Project description:Tumors that contain tumor-infiltrating lymphocytes (TIL) with tissue-resident memory T cells (TRM) features are associated with better patient prognoses. While CD8+ T cells that target tumors often fail to restrain tumor growth due to progressive T cell exhaustion, pathogen-specific TRM survey tissues and sustain protective capacity for years. We identified protein homeostasis (proteostasis)-related E3 ubiquitin ligase genes shared by TRM and progenitor-exhausted TIL (TPEX), that are lost as TIL become terminally-exhausted (TEX). Sustained ligase expression led to increased TCF1+ T cell accumulation and improved anti-tumor function and less T cell exhaustion in chronic infection. Loss-of-function in cancer models impaired TIL accumulation and function and altered T cell differentiation in response to acute infection. Low-input mass spectrometry revealed abundant expression of protein degradation pathways by TEX, yet they accumulated unfolded proteins. Ligase overexpression rescued unfolded protein accumulation in TEX, demonstrating their functional contribution to proteostasis. Ligase overexpression in combination with immune checkpoint blockade led to improved survival from murine melanoma, demonstrating that the relationship between proteostasis and T cell differentiation opens up new avenues for cancer immunotherapy.
2026-04-21 | PXD063865 | Pride
Project description:Tumors that contain tumor-infiltrating lymphocytes (TIL) with tissue-resident memory T cells (TRM) features are associated with better patient prognoses. While CD8+ T cells that target tumors often fail to restrain tumor growth due to progressive T cell exhaustion, pathogen-specific TRM survey tissues and sustain protective capacity for years. We identified protein homeostasis (proteostasis)-related E3 ubiquitin ligase genes shared by TRM and progenitor-exhausted TIL (TPEX), that are lost as TIL become terminally-exhausted (TEX). Sustained ligase expression led to increased TCF1+ T cell accumulation and improved anti-tumor function and less T cell exhaustion in chronic infection. Loss-of-function alleles in T cells challenged with cancer models impaired TIL accumulation and function and altered T cell differentiation in response to acute infection. Mass spectrometry revealed abundant expression of protein degradation pathways by TEX, yet they accumulated unfolded proteins. Ligase overexpression rescued unfolded protein accumulation in TEX, demonstrating their functional contribution to proteostasis. Ligase overexpression in combination with immune checkpoint blockade led to improved survival from murine melanoma, demonstrating that the relationship between proteostasis and T cell differentiation opens up new avenues for cancer immunotherapy.
2026-04-30 | PXD067417 | Pride
Project description:Tumors that contain tumor-infiltrating lymphocytes (TIL) with tissue-resident memory T cells (TRM) features are associated with better patient prognoses. While CD8+ T cells that target tumors often fail to restrain tumor growth due to progressive T cell exhaustion, pathogen-specific TRM survey tissues and sustain protective capacity for years. We identified protein homeostasis (proteostasis)-related E3 ubiquitin ligase genes shared by TRM and progenitor-exhausted TIL (TPEX), that are lost as TIL become terminally-exhausted (TEX). Sustained ligase expression led to increased TCF1+ T cell accumulation and improved anti-tumor function and less T cell exhaustion in chronic infection. Loss-of-function in cancer models impaired TIL accumulation and function and altered T cell differentiation in response to acute infection. Low-input mass spectrometry revealed abundant expression of protein degradation pathways by TEX, yet they accumulated unfolded proteins. Ligase overexpression rescued unfolded protein accumulation in TEX, demonstrating their functional contribution to proteostasis. Ligase overexpression in combination with immune checkpoint blockade led to improved survival from murine melanoma, demonstrating that the relationship between proteostasis and T cell differentiation opens up new avenues for cancer immunotherapy.
2026-04-21 | PXD070932 | Pride
Project description:Tissue-resident memory CD8+ T cells (Trm) are positioned at common sites of pathogen exposure where they elicit rapid and robust protective immune responses. However, the molecular signals controlling Trm differentiation and homeostasis are not fully understood. Here we show that mouse Trm precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory populations at the levels of gene expression and chromatin accessibility. Exploiting computational and functional RNAi in vivo screens, we identified the transcription factor (TF) Runx3 as a key regulator of Trm differentiation and homeostasis. Runx3 was required to establish Trm populations in diverse tissue environments and supported expression of critical tissue-residency genes while suppressing genes associated with tissue egress and recirculation. Analysis of the accessibility of Runx3 target genes in Trm-precursor cells revealed a distinct regulatory role for Runx3 in controlling Trm differentiation despite relatively widespread and uniform expression among all CD8+ T cell subsets. Further, we show that human and murine tumor-infiltrating lymphocytes (TIL) share a core tissue-residency gene-expression signature with Trm. In a mouse model of adoptive T cell therapy for melanoma, Runx3-deficient CD8+ TIL failed to accumulate in tumors, resulting in greater rates of tumor growth and mortality. Conversely, overexpression of Runx3 enhanced TIL abundance, delayed tumor growth, and prolonged survival. In addition to establishing Runx3 as a central regulator of Trm differentiation, these results provide novel insight into the signals that promote T cell residency in tissues, which could be leveraged to enhance vaccine efficacy or adoptive cell therapy treatments that target cancer.
2017-12-15 | GSE108092 | GEO
Project description:Tissue-resident memory CD8+ T cells (Trm) are positioned at common sites of pathogen exposure where they elicit rapid and robust protective immune responses. However, the molecular signals controlling Trm differentiation and homeostasis are not fully understood. Here we show that mouse Trm precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory populations at the levels of gene expression and chromatin accessibility. Exploiting computational and functional RNAi in vivo screens, we identified the transcription factor (TF) Runx3 as a key regulator of Trm differentiation and homeostasis. Runx3 was required to establish Trm populations in diverse tissue environments and supported expression of critical tissue-residency genes while suppressing genes associated with tissue egress and recirculation. Analysis of the accessibility of Runx3 target genes in Trm-precursor cells revealed a distinct regulatory role for Runx3 in controlling Trm differentiation despite relatively widespread and uniform expression among all CD8+ T cell subsets. Further, we show that human and murine tumor-infiltrating lymphocytes (TIL) share a core tissue-residency gene-expression signature with Trm. In a mouse model of adoptive T cell therapy for melanoma, Runx3-deficient CD8+ TIL failed to accumulate in tumors, resulting in greater rates of tumor growth and mortality. Conversely, overexpression of Runx3 enhanced TIL abundance, delayed tumor growth, and prolonged survival. In addition to establishing Runx3 as a central regulator of Trm differentiation, these results provide novel insight into the signals that promote T cell residency in tissues, which could be leveraged to enhance vaccine efficacy or adoptive cell therapy treatments that target cancer.
2017-12-15 | GSE107373 | GEO
Project description:CD8+ memory T cells are critical components of protective immunity to intracellular pathogens and tumors. While many memory CD8+ T cells recirculate throughout the body, others remain lodged in tissues and guard common sites of pathogen entry. Contributions of the specific tissue environment to tissue-resident memory T cell (Trm) differentiation and homeostasis have been implicated but are not well understood. Here, we define the diversity of gene expression and genome accessibility by mouse CD8+ Trm populations in distinct organs and identify molecules critical for Trm generated in response to acute viral infection. We find that CD8+ TRM across different tissues possess both shared and tissue-specific transcriptional and epigenetic signatures. Notably, Trm in the intestine and salivary gland express TGFb-induced genes and are maintained by ongoing TGFb signaling while those in the fat, kidney, and liver are not. By constructing transcriptional-regulatory networks for each Trm population, we identify the repressor Hic1 as a critical regulator of Trm differentiation, particularly for Trm of the small intestine. This study provides a framework for understanding how Trm adapt to distinct tissue environments and identifies tissue-specific transcriptional regulators that mediate these adaptations, informing strategies to enhance protective memory responses at the sites most vulnerable to infection.
2022-04-18 | GSE182271 | GEO
Project description:Tissue-resident memory CD8+ T cells (TRM) constitute a non-circulating memory T cell subset that provides early protection against re-infection. However, how TRM arise from antigen-triggered T cells has remained unclear. Exploiting the TRM-restricted expression of Hobit, we developed TRM reporter/deleter mice to study TRM differentiation. We found that Hobit was upregulated in a subset of LCMV-specific T cells located within peripheral tissues during the effector phase of the immune response. These Hobit+ effector T cells were identified as TRM precursors, given that their depletion substantially decreased TRM development, but not the formation of circulating memory T cells. Adoptive transfer experiments of Hobit+ effector T cells corroborated their biased contribution to the TRM lineage. Transcriptional profiling of Hobit+ effector T cells underlined the early establishment of TRM properties including downregulation of tissue exit receptors and upregulation of TRM-associated molecules. Importantly, we identified Eomes as a key factor instructing the early bifurcation of circulating and resident lineages. These findings establish that commitment of TRM occurs early in antigen-driven T cell differentiation and reveal the molecular mechanisms underlying this differentiation pathway.
2021-08-19 | GSE182343 | GEO
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