TNFR2 ligation in human T regulatory cells enhances IL2-induced cell proliferation through the non-canonical NF-κB pathway
Human T regulatory cells (T regs) express high levels of TNF receptor 2 (TNFR2). Ligation of TNFR2 with TNF, which can recognise both TNFR1 and TNFR2, or with a TNFR2-selective binding molecule, DARPin 18 (D18) activates canonical NF-κB signalling, assessed by IκBα degradation, and the magnitude of...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Publishing Group
2018
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| _version_ | 1826264225871298560 |
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| author | Wang, J Ferreira, R Lu, W Farrow, S Downes, K Jermutus, L Minter, R Al-Lamki, RS Pober, JS Bradley, JR |
| author_facet | Wang, J Ferreira, R Lu, W Farrow, S Downes, K Jermutus, L Minter, R Al-Lamki, RS Pober, JS Bradley, JR |
| author_sort | Wang, J |
| collection | OXFORD |
| description | Human T regulatory cells (T regs) express high levels of TNF receptor 2 (TNFR2). Ligation of TNFR2 with TNF, which can recognise both TNFR1 and TNFR2, or with a TNFR2-selective binding molecule, DARPin 18 (D18) activates canonical NF-κB signalling, assessed by IκBα degradation, and the magnitude of the response correlates with the level of TNFR2 expression. RNA-seq analysis of TNF- or D18-treated human T regs revealed that TNFR2 ligation induces transcription of NFKB2 and RELB, encoding proteins that form the non-canonical NF-κB transcription factor. In combination with IL2, D18 treatment is specific for T regs in (1) stabilising NF-κB-inducing kinase protein, the activator of non-canonical NF-κB signalling, (2) inducing translocation of RelB from cytosol to nucleus, (3) increasing cell cycle entry, and (4) increasing cell numbers. However, the regulatory function of the expanded T regs is unaltered. Inhibition of RelB nuclear translocation blocks the proliferative response. We conclude that ligation of TNFR2 by D18 enhances IL2-induced T regs proliferation and expansion in cell number through the non-canonical NF-κB pathway. |
| first_indexed | 2024-03-06T20:04:22Z |
| format | Journal article |
| id | oxford-uuid:286dbc75-47a4-4a77-b8d6-71f270f86a7f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:04:22Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:286dbc75-47a4-4a77-b8d6-71f270f86a7f2022-03-26T12:12:52ZTNFR2 ligation in human T regulatory cells enhances IL2-induced cell proliferation through the non-canonical NF-κB pathwayJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:286dbc75-47a4-4a77-b8d6-71f270f86a7fEnglishSymplectic Elements at OxfordNature Publishing Group2018Wang, JFerreira, RLu, WFarrow, SDownes, KJermutus, LMinter, RAl-Lamki, RSPober, JSBradley, JRHuman T regulatory cells (T regs) express high levels of TNF receptor 2 (TNFR2). Ligation of TNFR2 with TNF, which can recognise both TNFR1 and TNFR2, or with a TNFR2-selective binding molecule, DARPin 18 (D18) activates canonical NF-κB signalling, assessed by IκBα degradation, and the magnitude of the response correlates with the level of TNFR2 expression. RNA-seq analysis of TNF- or D18-treated human T regs revealed that TNFR2 ligation induces transcription of NFKB2 and RELB, encoding proteins that form the non-canonical NF-κB transcription factor. In combination with IL2, D18 treatment is specific for T regs in (1) stabilising NF-κB-inducing kinase protein, the activator of non-canonical NF-κB signalling, (2) inducing translocation of RelB from cytosol to nucleus, (3) increasing cell cycle entry, and (4) increasing cell numbers. However, the regulatory function of the expanded T regs is unaltered. Inhibition of RelB nuclear translocation blocks the proliferative response. We conclude that ligation of TNFR2 by D18 enhances IL2-induced T regs proliferation and expansion in cell number through the non-canonical NF-κB pathway. |
| spellingShingle | Wang, J Ferreira, R Lu, W Farrow, S Downes, K Jermutus, L Minter, R Al-Lamki, RS Pober, JS Bradley, JR TNFR2 ligation in human T regulatory cells enhances IL2-induced cell proliferation through the non-canonical NF-κB pathway |
| title | TNFR2 ligation in human T regulatory cells enhances IL2-induced cell proliferation through the non-canonical NF-κB pathway |
| title_full | TNFR2 ligation in human T regulatory cells enhances IL2-induced cell proliferation through the non-canonical NF-κB pathway |
| title_fullStr | TNFR2 ligation in human T regulatory cells enhances IL2-induced cell proliferation through the non-canonical NF-κB pathway |
| title_full_unstemmed | TNFR2 ligation in human T regulatory cells enhances IL2-induced cell proliferation through the non-canonical NF-κB pathway |
| title_short | TNFR2 ligation in human T regulatory cells enhances IL2-induced cell proliferation through the non-canonical NF-κB pathway |
| title_sort | tnfr2 ligation in human t regulatory cells enhances il2 induced cell proliferation through the non canonical nf κb pathway |
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