NF-κB protects NKT cells from tumor necrosis factor receptor 1-induced death
Semi-invariant natural killer T (NKT) cells are innate-like lymphocytes with immunoregulatory properties. NKT cell survival during development requires signal processing by activated RelA/NF-κB. Nonetheless, the upstream signal(s) integrated by NF-κB in developing NKT cells remains incompletely defi...
| Asıl Yazarlar: | , , , , , , , |
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| Materyal Türü: | Journal article |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
Nature Publishing Group
2017
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| _version_ | 1826272264617721856 |
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| author | Kumar, A Gordy, LE Bezbradica, JS Stanic, AK Hill, TM Boothby, MR Van Kaer, L Joyce, S |
| author_facet | Kumar, A Gordy, LE Bezbradica, JS Stanic, AK Hill, TM Boothby, MR Van Kaer, L Joyce, S |
| author_sort | Kumar, A |
| collection | OXFORD |
| description | Semi-invariant natural killer T (NKT) cells are innate-like lymphocytes with immunoregulatory properties. NKT cell survival during development requires signal processing by activated RelA/NF-κB. Nonetheless, the upstream signal(s) integrated by NF-κB in developing NKT cells remains incompletely defined. We show that the introgression of Bcl-xL-coding Bcl2l1 transgene into NF-κB signalling-deficient IκBΔN transgenic mouse rescues NKT cell development and differentiation in this mouse model. We reasoned that NF-κB activation was protecting developing NKT cells from death signals emanating either from high affinity agonist recognition by the T cell receptor (TCR) or from a death receptor, such as tumor necrosis factor receptor 1 (TNFR1) or Fas. Surprisingly, the single and combined deficiency in PKC-θ or CARMA-1-the two signal transducers at the NKT TCR proximal signalling node-only partially recapitulated the NKT cell deficiency observed in IκBΔN tg mouse. Accordingly, introgression of the Bcl2l1 transgene into PKC-θ null mouse failed to rescue NKT cell development. Instead, TNFR1-deficiency, but not the Fas-deficiency, rescued NKT cell development in IκBΔN tg mice. Consistent with this finding, treatment of thymocytes with an antagonist of the inhibitor of κB kinase -which blocks downstream NF-κB activation- sensitized NKT cells to TNF-α-induced cell death in vitro. Hence, we conclude that signal integration by NF-κB protects developing NKT cells from death signals emanating from TNFR1, but not from the NKT TCR or Fas. |
| first_indexed | 2024-03-06T22:09:49Z |
| format | Journal article |
| id | oxford-uuid:516b9fa1-b6e9-46ef-932e-a30208e18ba2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:09:49Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:516b9fa1-b6e9-46ef-932e-a30208e18ba22022-03-26T16:19:26ZNF-κB protects NKT cells from tumor necrosis factor receptor 1-induced deathJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:516b9fa1-b6e9-46ef-932e-a30208e18ba2EnglishSymplectic Elements at OxfordNature Publishing Group2017Kumar, AGordy, LEBezbradica, JSStanic, AKHill, TMBoothby, MRVan Kaer, LJoyce, SSemi-invariant natural killer T (NKT) cells are innate-like lymphocytes with immunoregulatory properties. NKT cell survival during development requires signal processing by activated RelA/NF-κB. Nonetheless, the upstream signal(s) integrated by NF-κB in developing NKT cells remains incompletely defined. We show that the introgression of Bcl-xL-coding Bcl2l1 transgene into NF-κB signalling-deficient IκBΔN transgenic mouse rescues NKT cell development and differentiation in this mouse model. We reasoned that NF-κB activation was protecting developing NKT cells from death signals emanating either from high affinity agonist recognition by the T cell receptor (TCR) or from a death receptor, such as tumor necrosis factor receptor 1 (TNFR1) or Fas. Surprisingly, the single and combined deficiency in PKC-θ or CARMA-1-the two signal transducers at the NKT TCR proximal signalling node-only partially recapitulated the NKT cell deficiency observed in IκBΔN tg mouse. Accordingly, introgression of the Bcl2l1 transgene into PKC-θ null mouse failed to rescue NKT cell development. Instead, TNFR1-deficiency, but not the Fas-deficiency, rescued NKT cell development in IκBΔN tg mice. Consistent with this finding, treatment of thymocytes with an antagonist of the inhibitor of κB kinase -which blocks downstream NF-κB activation- sensitized NKT cells to TNF-α-induced cell death in vitro. Hence, we conclude that signal integration by NF-κB protects developing NKT cells from death signals emanating from TNFR1, but not from the NKT TCR or Fas. |
| spellingShingle | Kumar, A Gordy, LE Bezbradica, JS Stanic, AK Hill, TM Boothby, MR Van Kaer, L Joyce, S NF-κB protects NKT cells from tumor necrosis factor receptor 1-induced death |
| title | NF-κB protects NKT cells from tumor necrosis factor receptor 1-induced death |
| title_full | NF-κB protects NKT cells from tumor necrosis factor receptor 1-induced death |
| title_fullStr | NF-κB protects NKT cells from tumor necrosis factor receptor 1-induced death |
| title_full_unstemmed | NF-κB protects NKT cells from tumor necrosis factor receptor 1-induced death |
| title_short | NF-κB protects NKT cells from tumor necrosis factor receptor 1-induced death |
| title_sort | nf κb protects nkt cells from tumor necrosis factor receptor 1 induced death |
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