Stem-like potential of T cells in infection and cancer is regulated by ID3
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ABSTRACT:
PROVIDER: PRJNA1162458 | ENA |
REPOSITORIES: ENA
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Project description:Memory CD8+ T cells and precursors of exhausted T (Tpex) cells are important therapeutic targets due to their stem-like potential that allows them to self-renew while also giving rise to large numbers of effector T cells that can provide protection from infection or uncontrolled tumor growth. Identifying T cells with stem-like potential and understanding their molecular regulation is therefore critical to improve a wide range of T cell-focused therapies ranging from vaccination to checkpoint inhibitor and chimeric antigen receptor T cell therapies. Here, we identify memory T cells based on expression of the transcriptional regulator ID3 while lacking expression of the chemokine receptor CXCR6 with superior stem-like potential to sustain T cell responses during chronic infection. Mechanistically, ID3 regulated a transcriptional network including Myb, Sell and cKit that promoted T cell stemness that was specifically required during ongoing T cell receptor stimulation. T cells lacking ID3 were unable to sustain a long-term response to chronic infection but capable of efficiently responding to acute infection. Overall, we identify a critical role for ID3 in promoting functional and long-lasting T cell responses specifically to chronic infections and highlight ID3-expressing stem-like memory T cells as a promising immunotherapeutic target to improve immune responses in chronic infections or tumors.
2024-12-13 | GSE277451 | GEO
Project description:Memory CD8+ T cells and precursors of exhausted T (Tpex) cells are important therapeutic targets due to their stem-like potential that allows them to self-renew while also giving rise to large numbers of effector T cells that can provide protection from infection or uncontrolled tumor growth. Identifying T cells with stem-like potential and understanding their molecular regulation is therefore critical to improve a wide range of T cell-focused therapies ranging from vaccination to checkpoint inhibitor and chimeric antigen receptor T cell therapies. Here, we identify memory T cells based on expression of the transcriptional regulator ID3 while lacking expression of the chemokine receptor CXCR6 with superior stem-like potential to sustain T cell responses during chronic infection. Mechanistically, ID3 regulated a transcriptional network including Myb, Sell and cKit that promoted T cell stemness that was specifically required during ongoing T cell receptor stimulation. T cells lacking ID3 were unable to sustain a long-term response to chronic infection but capable of efficiently responding to acute infection. Overall, we identify a critical role for ID3 in promoting functional and long-lasting T cell responses specifically to chronic infections and highlight ID3-expressing stem-like memory T cells as a promising immunotherapeutic target to improve immune responses in chronic infections or tumors.
2024-12-14 | GSE224367 | GEO
Project description:Memory CD8+ T cells and precursors of exhausted T (Tpex) cells are important therapeutic targets due to their stem-like potential that allows them to self-renew while also giving rise to large numbers of effector T cells that can provide protection from infection or uncontrolled tumor growth. Identifying T cells with stem-like potential and understanding their molecular regulation is therefore critical to improve a wide range of T cell-focused therapies ranging from vaccination to checkpoint inhibitor and chimeric antigen receptor T cell therapies. Here, we identify memory T cells based on expression of the transcriptional regulator ID3 while lacking expression of the chemokine receptor CXCR6 with superior stem-like potential to sustain T cell responses during chronic infection. Mechanistically, ID3 regulated a transcriptional network including Myb, Sell and cKit that promoted T cell stemness that was specifically required during ongoing T cell receptor stimulation. T cells lacking ID3 were unable to sustain a long-term response to chronic infection but capable of efficiently responding to acute infection. Overall, we identify a critical role for ID3 in promoting functional and long-lasting T cell responses specifically to chronic infections and highlight ID3-expressing stem-like memory T cells as a promising immunotherapeutic target to improve immune responses in chronic infections or tumors.
2024-12-13 | GSE226030 | GEO
Project description:ID3 defines T cells with stem-like potential and sustains their response to chronic infection
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Project description:During an immune response, CD8 T cells fall along a gradient of memory potential, but the regulators of these fate decsisions are not well understood. We utlized Id3-GFP and Id2-YFP reporter mice to elucidate the role of Id3 and Id2 during early CD8 T cell differentiation by gene expression. Id3-GFP hi Id2-YFP int or Id3-GFP lo Id2-YFP hi OT-I cells were sorted into trizol at day 6 of VSV-OVA infection and analyzed by microarray
2011-10-06 | E-GEOD-32675 | biostudies-arrayexpress
Project description:ID3 and c-Kit define the stem-like potential of T cells and their response to chronic infection and cancer
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Project description:Murine WT and Id3-/- adult neural stem cells were plated as dissociated cells and treated for 3 hours with rhBMP-2 under differentiation conditions to mimic traumatic brain injury in vitro
2015-09-30 | E-MTAB-2455 | biostudies-arrayexpress
Project description:During an immune response, CD8 T cells fall along a gradient of memory potential, but the regulators of these fate decsisions are not well understood. We utlized Id3-GFP and Id2-YFP reporter mice to elucidate the role of Id3 and Id2 during early CD8 T cell differentiation by gene expression.
2011-10-07 | GSE32675 | GEO
Project description:Macrophage activation is controlled by a balance between activating and inhibitory receptors which protect normal tissues from excessive damage during infection but promote tumor growth and metastasis in cancer. We report here that the Kupffer cell (KC)-lineage determining factor ID3 controls this balance and selectively endows KC with the ability to phagocytose live tumor cells and orchestrate the recruitment, proliferation, and activation of NK and CD8 T lymphoid effector cells in the liver to restrict the growth of a variety of tumors. ID3 shifts the macrophage inhibitory/activating receptor balance to unleash the phagocytic and lymphoid response, at least in part by buffering binding of the transcription factors ELK1 and E2A at the Sirpα locus. Furthermore, loss- and gain-of-function experiments demonstrate that ID3 is sufficient to confer this potent anti-tumor activity to mouse bone marrow derived macrophages and human induced pluripotent stem cells derived macrophages. Expression of ID3 is therefore necessary and sufficient to endow macrophages with the ability to form an efficient anti-tumor niche, which could be harnessed for cell therapy in cancer.
2023-11-14 | GSE234638 | GEO
Project description:The molecular mechanisms by which signaling via transforming growth factor-β (TGF-β) and interleukin 4 (IL-4) control the differentiation of IL-9-producing CD4+ helper T cells (TH9 cells) remain incompletely understood. We found here that the DNA-binding inhibitor Id3 regulated TH9 cell differentiation, as deletion of Id3 increased IL-9 production from CD4+ T cells. Mechanistically, TGF-β1 and IL-4 downregulated Id3 expression, and this process required the kinase TAK1. A reduction in Id3 expression enhanced binding of the transcription factors E2A and GATA-3 to the Il9 promoter region, which promoted Il9 transcription. Notably, Id3’s control of TH9 differentiation regulated anti-tumor immunity in an experimental melanoma-bearing model in vivo and also in human CD4+ T cells in vitro. Thus, our study reveals a previously unrecognized TAK1–Id3–E2A–GATA-3 pathway that regulates TH9 differentiation.
2015-08-14 | GSE72051 | GEO