Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours
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ABSTRACT:
PROVIDER: PRJNA419960 | ENA |
REPOSITORIES: ENA
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Project description: Not available
| S-EPMC5747964 | biostudies-literature
Project description:Pattens of tissue-residency differs between CD4+ and CD8+ memory T cells in evironmentally exposed organs. The lineage-controlling transcription factor Runx3, expressed in CD8+ T cells, is responsible for shaping a tissue-resident gene network in response to the cytokine TGF-b. While the lack of Runx3 by CD4+ T cells precludes these transcriptional changes, Runx3-overexpression in CD+ T cells enable phenotypical, transcriptional and functional changes to allow residency.
2022-05-24 | GSE182511 | 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:This SuperSeries is composed of the SubSeries listed below.
2017-12-15 | GSE107395 | 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:Runx3 drives a tissue-residency program that is absent in CD4+ T cells
| PRJNA816144 | ENA
Project description:In this study, RUNX3 expression was analyzed in normal and malignant haematopoiesis and the impact of its dysregulation on myelopoiesis was further determined. We found that RUNX3 was highly expressed in haematopoietic progenitors, with its levels reducing towards granulocytic differentiation. In AML, RUNX3 was overexpressed across all different subtypes except in core binding factor AML where it was downregulated. RUNX3 overexpression in human haematopoietic stem and progenitor cells (HSPC) inhibited myeloid development, particularly granulopoiesis. Further RNA-sequencing studies showed that RUNX3 overexpression downregulates key hematopoietic genes, while upregulating certain lymphoid genes. Overall, this study suggests that increased RUNX3 expression could contribute to the myeloid block characteristic of AML by possibly driving a competing transcriptional program favoring the lymphoid fate.
2022-04-13 | GSE181059 | GEO
Project description:To determine if ectopic expression of Runx3 can correct deficient lymphoid output in aged HSCs, we examine the chromatin profile of aged HSC transduced with control or Runx3-expressing lentivirus.
2023-02-22 | GSE219004 | 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:Runx3 drives a tissue-residency program that is absent in CD4+ T cells [RNA-seq]
| PRJNA756546 | ENA