ID3 and c-Kit define the stem-like potential of T cells and their response to chronic infection and cancer
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PROVIDER: PRJNA938396 | 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 | GSE226030 | 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 | GSE277451 | 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:Foxp3+ regulatory T (TR) cells are phenotypically and functionally diverse, and broadly distributed in lymphoid and non-lymphoid tissues. However, the pathways guiding the differentiation of tissue-resident TR populations have not been well defined. By regulating E-protein function, Id3 controls the differentiation of CD8+ effector T cells and is essential for TR maintenance and function. We show that dynamic expression of Id3 helps define three distinct mouse TR populations, Id3+CD62LhiCD44lo central (c)TR, Id3+CD62LloCD44hi effector (e)TR and Id3- eTR. Adoptive transfer experiments and transcriptome analyses support a stepwise model of differentiation from Id3+ cTR to Id3+ eTR to Id3- eTR. Furthermore, Id3- eTR have high expression of functional inhibitory markers and a transcriptional signature of tissue-resident TR. Accordingly, Id3- eTR are highly enriched in non-lymphoid organs, but virtually absent from blood and lymph. Thus, we propose that tissue-resident TR develop in a multi-step process associated with Id3 downregulation.
2018-11-16 | GSE122593 | GEO
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:Previous studies have demonstrated that E-proteins induce AID expression in activated B cells. Here we have examined the role of Id3 in germinal center (GC) cells. We found that Id3 expression is high in follicular B-lineage cells but declines in GC cells. Immunized mice depleted for Id3 expression displayed a block in germinal center B cell maturation, showed reduced numbers of marginal zone B cells and class switched cells, were associated with decreased antibody titers and lower numbers of plasma cells. In vitro Id3-depleted B cells displayed a defect in class switch recombination. Whereas AID levels were not altered in Id3-depleted activated B cells, the expression of a subset of genes encoding for signaling components of antigen receptor, cytokine receptor and chemokine receptor mediated signaling was significantly impaired. We propose that during the GC reaction Id3 levels decline to activate the expression of genes encoding for signaling components that mediate B cell receptor and or cytokine-mediated signaling to promote the differentiation of GC B cells.
2016-08-18 | GSE84374 | GEO
Project description:Stem-like potential of T cells in infection and cancer is regulated by ID3
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Project description:Previously it has been shown that Id3 can act as an apoptosis-inducer gene in immortalized human keratinocytes. To further investigate the role of Id3 in the progression of skin cancer, the role of Id3 in A431 cells is investigated through ectopic induction of Id3. Microarray analysis is used to guide us the genes and pathways that are significantly altered after Id3 induction.
2015-06-30 | GSE64535 | GEO