PD-1 and CTLA-4 exert additive control of effector regulatory T cells at homeostasis
Copyright © 2023 Pereira, Lanzar, Clark, Hart, Douglas, Shallberg, O’Dea, Christian and Hunter..
At homeostasis, a substantial proportion of Foxp3+ T regulatory cells (Tregs) have an activated phenotype associated with enhanced TCR signals and these effector Treg cells (eTregs) co-express elevated levels of PD-1 and CTLA-4. Short term in vivo blockade of the PD-1 or CTLA-4 pathways results in increased eTreg populations, while combination blockade of both pathways had an additive effect. Mechanistically, combination blockade resulted in a reduction of suppressive phospho-SHP2 Y580 in eTreg cells which was associated with increased proliferation, enhanced production of IL-10, and reduced dendritic cell and macrophage expression of CD80 and MHC-II. Thus, at homeostasis, PD-1 and CTLA-4 function additively to regulate eTreg function and the ability to target these pathways in Treg cells may be useful to modulate inflammation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Frontiers in immunology - 14(2023) vom: 01., Seite 997376 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pereira, Joseph A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.03.2023 Date Revised 18.04.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2023.997376 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354652044 |
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| 500 | |a Date Revised 18.04.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Pereira, Lanzar, Clark, Hart, Douglas, Shallberg, O’Dea, Christian and Hunter. | ||
| 520 | |a At homeostasis, a substantial proportion of Foxp3+ T regulatory cells (Tregs) have an activated phenotype associated with enhanced TCR signals and these effector Treg cells (eTregs) co-express elevated levels of PD-1 and CTLA-4. Short term in vivo blockade of the PD-1 or CTLA-4 pathways results in increased eTreg populations, while combination blockade of both pathways had an additive effect. Mechanistically, combination blockade resulted in a reduction of suppressive phospho-SHP2 Y580 in eTreg cells which was associated with increased proliferation, enhanced production of IL-10, and reduced dendritic cell and macrophage expression of CD80 and MHC-II. Thus, at homeostasis, PD-1 and CTLA-4 function additively to regulate eTreg function and the ability to target these pathways in Treg cells may be useful to modulate inflammation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) | |
| 650 | 4 | |a IL-10 (Interleukin 10) | |
| 650 | 4 | |a PD-1 - PD-L1 axis | |
| 650 | 4 | |a checkpoint blockade immunotherapy | |
| 650 | 4 | |a eTreg cells | |
| 650 | 4 | |a homeostatic regulation | |
| 650 | 4 | |a immune suppression | |
| 650 | 4 | |a treg - regulatory T cell | |
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| 700 | 1 | |a Lanzar, Zachary |e verfasserin |4 aut | |
| 700 | 1 | |a Clark, Joseph T |e verfasserin |4 aut | |
| 700 | 1 | |a Hart, Andrew P |e verfasserin |4 aut | |
| 700 | 1 | |a Douglas, Bonnie B |e verfasserin |4 aut | |
| 700 | 1 | |a Shallberg, Lindsey |e verfasserin |4 aut | |
| 700 | 1 | |a O'Dea, Keenan |e verfasserin |4 aut | |
| 700 | 1 | |a Christian, David A |e verfasserin |4 aut | |
| 700 | 1 | |a Hunter, Christopher A |e verfasserin |4 aut | |
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