TGFβ limits Myc-dependent TCR-induced metabolic reprogramming in CD8+ T cells Article Swipe
Helen Carrasco Hope
,
Gabriella Pickersgill
,
Pierpaolo Ginefra
,
Nicola Vannini
,
Graham P. Cook
,
Robert J. Salmond
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.913184
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.913184
T cell activation is dependent upon the integration of antigenic, co-stimulatory and cytokine-derived signals and the availability and acquisition of nutrients from the environment. Furthermore, T cell activation is accompanied by reprogramming of cellular metabolism to provide the energy and building blocks for proliferation, differentiation and effector function. Transforming growth factor β (TGFβ) has pleiotropic effects on T cell populations, having both an essential role in the maintenance of immune tolerance but also context-dependent pro-inflammatory functions. We set out to define the mechanisms underpinning the suppressive effects of TGFβ on mouse CD8 + T cell activation. RNA-sequencing analysis of TCR-stimulated T cells determined that Myc-regulated genes were highly enriched within gene sets downregulated by TGFβ. Functional analysis demonstrated that TGFβ impeded TCR-induced upregulation of amino acid transporter expression, amino acid uptake and protein synthesis. Furthermore, TCR-induced upregulation of Myc-dependent glycolytic metabolism was substantially inhibited by TGFβ treatment with minimal effects on mitochondrial respiration. Thus, our data suggest that inhibition of Myc-dependent metabolic reprogramming represents a major mechanism underpinning the suppressive effects of TGFβ on CD8 + T cell activation.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2022.913184
- https://www.frontiersin.org/articles/10.3389/fimmu.2022.913184/pdf
- OA Status
- gold
- Cited By
- 8
- References
- 36
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4287921408
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4287921408Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3389/fimmu.2022.913184Digital Object Identifier
- Title
-
TGFβ limits Myc-dependent TCR-induced metabolic reprogramming in CD8+ T cellsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-07-26Full publication date if available
- Authors
-
Helen Carrasco Hope, Gabriella Pickersgill, Pierpaolo Ginefra, Nicola Vannini, Graham P. Cook, Robert J. SalmondList of authors in order
- Landing page
-
https://doi.org/10.3389/fimmu.2022.913184Publisher landing page
- PDF URL
-
https://www.frontiersin.org/articles/10.3389/fimmu.2022.913184/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.frontiersin.org/articles/10.3389/fimmu.2022.913184/pdfDirect OA link when available
- Concepts
-
Reprogramming, T-cell receptor, Cytotoxic T cell, Cell biology, CD8, Cancer research, Biology, T cell, Immunology, Immune system, Genetics, Gene, In vitroTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
8Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 5, 2024: 1, 2023: 1, 2022: 1Per-year citation counts (last 5 years)
- References (count)
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36Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.Myc-dependent | 138, 160 |
| abstract_inverted_index.Myc-regulated | 104 |
| abstract_inverted_index.downregulated | 112 |
| abstract_inverted_index.mitochondrial | 151 |
| abstract_inverted_index.reprogramming | 31, 162 |
| abstract_inverted_index.substantially | 142 |
| abstract_inverted_index.RNA-sequencing | 96 |
| abstract_inverted_index.TCR-stimulated | 99 |
| abstract_inverted_index.co-stimulatory | 10 |
| abstract_inverted_index.proliferation, | 43 |
| abstract_inverted_index.differentiation | 44 |
| abstract_inverted_index.cytokine-derived | 12 |
| abstract_inverted_index.pro-inflammatory | 74 |
| abstract_inverted_index.context-dependent | 73 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5063439378, https://openalex.org/A5087416182 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 6 |
| corresponding_institution_ids | https://openalex.org/I130828816, https://openalex.org/I2801331674, https://openalex.org/I4210117758, https://openalex.org/I97565354 |
| citation_normalized_percentile.value | 0.75614598 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |