The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues
After exiting the thymus, Foxp3+ regulatory T (Treg) cells undergo further differentiation in the periphery, resulting in the generation of mature, fully suppressive effector (e)Treg cells in a process dependent on TCR signaling and the transcription factor IRF4. Here, we show that tumor necrosis fa...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-09-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471731210X |
| _version_ | 1818307426743484416 |
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| author | Ajithkumar Vasanthakumar Yang Liao Peggy Teh Maria F. Pascutti Anna E. Oja Alexandra L. Garnham Renee Gloury Jessica C. Tempany Tom Sidwell Eloy Cuadrado Paul Tuijnenburg Taco W. Kuijpers Najoua Lalaoui Lisa A. Mielke Vanessa L. Bryant Philip D. Hodgkin John Silke Gordon K. Smyth Martijn A. Nolte Wei Shi Axel Kallies |
| author_facet | Ajithkumar Vasanthakumar Yang Liao Peggy Teh Maria F. Pascutti Anna E. Oja Alexandra L. Garnham Renee Gloury Jessica C. Tempany Tom Sidwell Eloy Cuadrado Paul Tuijnenburg Taco W. Kuijpers Najoua Lalaoui Lisa A. Mielke Vanessa L. Bryant Philip D. Hodgkin John Silke Gordon K. Smyth Martijn A. Nolte Wei Shi Axel Kallies |
| author_sort | Ajithkumar Vasanthakumar |
| collection | DOAJ |
| description | After exiting the thymus, Foxp3+ regulatory T (Treg) cells undergo further differentiation in the periphery, resulting in the generation of mature, fully suppressive effector (e)Treg cells in a process dependent on TCR signaling and the transcription factor IRF4. Here, we show that tumor necrosis factor receptor superfamily (TNFRSF) signaling plays a crucial role in the development and maintenance of eTreg cells. TNFRSF signaling activated the NF-κB transcription factor RelA, which was required to maintain eTreg cells in lymphoid and non-lymphoid tissues, including RORγt+ Treg cells in the small intestine. In response to TNFRSF signaling, RelA regulated basic cellular processes, including cell survival and proliferation, but was dispensable for IRF4 expression or DNA binding, indicating that both pathways operated independently. Importantly, mutations in the RelA binding partner NF-κB1 compromised eTreg cells in humans, suggesting that the TNFRSF-NF-κB axis was required in a non-redundant manner to maintain eTreg cells in mice and humans. |
| first_indexed | 2024-12-13T06:58:12Z |
| format | Article |
| id | doaj.art-a6158e2926c7412c92b606577bc61e39 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T06:58:12Z |
| publishDate | 2017-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a6158e2926c7412c92b606577bc61e392022-12-21T23:56:00ZengElsevierCell Reports2211-12472017-09-0120122906292010.1016/j.celrep.2017.08.068The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid TissuesAjithkumar Vasanthakumar0Yang Liao1Peggy Teh2Maria F. Pascutti3Anna E. Oja4Alexandra L. Garnham5Renee Gloury6Jessica C. Tempany7Tom Sidwell8Eloy Cuadrado9Paul Tuijnenburg10Taco W. Kuijpers11Najoua Lalaoui12Lisa A. Mielke13Vanessa L. Bryant14Philip D. Hodgkin15John Silke16Gordon K. Smyth17Martijn A. Nolte18Wei Shi19Axel Kallies20Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, AustraliaDepartment of Medical Biology, University of Melbourne, Melbourne, AustraliaMolecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, AustraliaDepartment of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, the NetherlandsDepartment of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, the NetherlandsDepartment of Medical Biology, University of Melbourne, Melbourne, AustraliaMolecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, AustraliaDepartment of Medical Biology, University of Melbourne, Melbourne, AustraliaMolecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, AustraliaDepartment of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, the NetherlandsDepartment of Pediatric Hematology, Immunology, and Infectious Diseases, Emma Children’s Hospital, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, the NetherlandsDepartment of Pediatric Hematology, Immunology, and Infectious Diseases, Emma Children’s Hospital, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, the NetherlandsDepartment of Medical Biology, University of Melbourne, Melbourne, AustraliaMolecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, AustraliaDepartment of Medical Biology, University of Melbourne, Melbourne, AustraliaDepartment of Medical Biology, University of Melbourne, Melbourne, AustraliaDepartment of Medical Biology, University of Melbourne, Melbourne, AustraliaBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, AustraliaDepartment of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, the NetherlandsBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, AustraliaMolecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, AustraliaAfter exiting the thymus, Foxp3+ regulatory T (Treg) cells undergo further differentiation in the periphery, resulting in the generation of mature, fully suppressive effector (e)Treg cells in a process dependent on TCR signaling and the transcription factor IRF4. Here, we show that tumor necrosis factor receptor superfamily (TNFRSF) signaling plays a crucial role in the development and maintenance of eTreg cells. TNFRSF signaling activated the NF-κB transcription factor RelA, which was required to maintain eTreg cells in lymphoid and non-lymphoid tissues, including RORγt+ Treg cells in the small intestine. In response to TNFRSF signaling, RelA regulated basic cellular processes, including cell survival and proliferation, but was dispensable for IRF4 expression or DNA binding, indicating that both pathways operated independently. Importantly, mutations in the RelA binding partner NF-κB1 compromised eTreg cells in humans, suggesting that the TNFRSF-NF-κB axis was required in a non-redundant manner to maintain eTreg cells in mice and humans.http://www.sciencedirect.com/science/article/pii/S221112471731210XTNFRSF signalingeffector Treg cellsNF-κB/RelATCRIRF4tissue Treg cellsRORγt+ Treg cells |
| spellingShingle | Ajithkumar Vasanthakumar Yang Liao Peggy Teh Maria F. Pascutti Anna E. Oja Alexandra L. Garnham Renee Gloury Jessica C. Tempany Tom Sidwell Eloy Cuadrado Paul Tuijnenburg Taco W. Kuijpers Najoua Lalaoui Lisa A. Mielke Vanessa L. Bryant Philip D. Hodgkin John Silke Gordon K. Smyth Martijn A. Nolte Wei Shi Axel Kallies The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues Cell Reports TNFRSF signaling effector Treg cells NF-κB/RelA TCR IRF4 tissue Treg cells RORγt+ Treg cells |
| title | The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues |
| title_full | The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues |
| title_fullStr | The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues |
| title_full_unstemmed | The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues |
| title_short | The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues |
| title_sort | tnf receptor superfamily nf κb axis is critical to maintain effector regulatory t cells in lymphoid and non lymphoid tissues |
| topic | TNFRSF signaling effector Treg cells NF-κB/RelA TCR IRF4 tissue Treg cells RORγt+ Treg cells |
| url | http://www.sciencedirect.com/science/article/pii/S221112471731210X |
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