The transcriptional cofactor Tle3 programs resident memory CD8+T cells differentiation [scRNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE326375 | GEO | 2026/06/15
REPOSITORIES: GEO
Similar Datasets
Project description:Tissue-resident CD8+ T cells (CD8+ TRM) possess the ability to efficiently eliminate invading pathogens locally and are an essential component of the immune barrier. The upregulation of tissue residency-related genes and the downregulation of tissue egress-related genes are critical for the differentiation and long-term residency of CD8+ TRM. However, the coordinated regulatory mechanisms of these two transcriptional programs remain unclear. Tle3 is a transcriptional cofactor that promotes and maintains the differentiation of circulating memory CD8+ T cell subsets by cooperating with key transcription factors. However, its role in the differentiation of CD8+ TRM remains unknown. Our preliminary studies indicate that Tle3 promotes the differentiation of CD8+ TRM subsets in multiple tissues, including the lung, and serves as a key regulator of TRM differentiation. Transcriptomic analysis suggests that Tle3 regulates CD8+ TRM differentiation by promoting the expression of TRM-associated genes while suppressing tissue egress-related genes, highlighting its crucial role in establishing the transcriptional program of CD8+ TRM and balancing the expression of residency and egress-related genes. Nevertheless, the key downstream molecules regulated by Tle3 and how it coordinates different transcriptional networks remain unclear.
2026-06-15 | GSE326374 | GEO
Project description:Tissue-resident CD8+ T cells (CD8+ TRM) possess the ability to efficiently eliminate invading pathogens locally and are an essential component of the immune barrier. The upregulation of tissue residency-related genes and the downregulation of tissue egress-related genes are critical for the differentiation and long-term residency of CD8+ TRM. However, the coordinated regulatory mechanisms of these two transcriptional programs remain unclear. Tle3 is a transcriptional cofactor that promotes and maintains the differentiation of circulating memory CD8+ T cell subsets by cooperating with key transcription factors. However, its role in the differentiation of CD8+ TRM remains unknown. Our preliminary studies indicate that Tle3 promotes the differentiation of CD8+ TRM subsets in multiple tissues, including the lung, and serves as a key regulator of TRM differentiation. Transcriptomic analysis suggests that Tle3 regulates CD8+ TRM differentiation by promoting the expression of TRM-associated genes while suppressing tissue egress-related genes, highlighting its crucial role in establishing the transcriptional program of CD8+ TRM and balancing the expression of residency and egress-related genes. Nevertheless, the key downstream molecules regulated by Tle3 and how it coordinates different transcriptional networks remain unclear.
2026-06-15 | GSE326373 | GEO
Project description:Tissue-resident CD8+ T cells (CD8+ TRM) possess the ability to efficiently eliminate invading pathogens locally and are an essential component of the immune barrier. The upregulation of tissue residency-related genes and the downregulation of tissue egress-related genes are critical for the differentiation and long-term residency of CD8+ TRM. However, the coordinated regulatory mechanisms of these two transcriptional programs remain unclear. Tle3 is a transcriptional cofactor that promotes and maintains the differentiation of circulating memory CD8+ T cell subsets by cooperating with key transcription factors. However, its role in the differentiation of CD8+ TRM remains unknown. Our preliminary studies indicate that Tle3 promotes the differentiation of CD8+ TRM subsets in multiple tissues, including the lung, and serves as a key regulator of TRM differentiation. Transcriptomic analysis suggests that Tle3 regulates CD8+ TRM differentiation by promoting the expression of TRM-associated genes while suppressing tissue egress-related genes, highlighting its crucial role in establishing the transcriptional program of CD8+ TRM and balancing the expression of residency and egress-related genes. Nevertheless, the key downstream molecules regulated by Tle3 and how it coordinates different transcriptional networks remain unclear.
2026-06-15 | GSE326376 | GEO
Project description:Tissue-resident memory T (TRM) cells provide rapid and superior control of localized infections. The transcription factor Runx3 was recently identified as a master regulator of CD8+ T cell tissue residency. However, Runx3 also drives CD8+ T cell lineage commitment and is repressed in CD4+ T cells, raising the possibility that this transcription factor defines a form of tissue residency unique to the CD8+ T cell subset. Here, we show that as a direct consequence of Runx3-deficiency, CD4+ TRM cells in epithelia lack the TGFb-responsive transcriptional network that underpins CD8+ TRM cell residency. Ectopic Runx3 expression in CD4+ T cells rescued this transcriptional program to promote prolonged survival, decreased tissue egress and a microanatomical redistribution towards epithelial layers that combined, resulted in superior local immune protection. Our results thus reveal a mechanistic discordance between CD4+ and CD8+ TRM cell formation in barrier tissues that is controlled by Runx3. Consequently, CD4+ TRM cells are unable to adopt a type of tissue residency that is intrinsically accessible to the CD8+ TRM cell subset.
2022-05-24 | GSE198611 | 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.
2018-01-03 | GSE106107 | 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 responses1,2. 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 | GSE107289 | 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: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 responses1,2. 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 | GSE107281 | 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 responses1,2. 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 | GSE107278 | GEO