Carty, Fiona;
Layzell, Scott;
Barbarulo, Alessandro;
Islam, Farjana;
Webb, Louise V;
Seddon, Benedict;
(2023)
IKK promotes naïve T cell survival by repressing RIPK1-dependent apoptosis and activating NF-κB.
Science Signaling
, 16
(791)
, Article eabo4094. 10.1126/scisignal.abo4094.
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Abstract
The inhibitor of κB kinase (IKK) complex regulates the activation of the nuclear factor κB (NF-κB) family of transcription factors. In addition, IKK represses extrinsic cell death pathways dependent on receptor-interacting serine/threonine-protein kinase 1 (RIPK1) by directly phosphorylating this kinase. Here, we showed that peripheral naïve T cells in mice required the continued expression of IKK1 and IKK2 for their survival; however, the loss of these cells was only partially prevented when extrinsic cell death pathways were blocked by either deleting Casp8 (which encodes the apoptosis-inducing caspase 8) or inhibiting the kinase activity of RIPK1. Inducible deletion of Rela (which encodes the NF-κB p65 subunit) in mature CD4+ T cells also resulted in loss of naïve CD4+ T cells and in reduced abundance of the interleukin-7 receptor (IL-7R) encoded by the NF-κB target Il7r, revealing an additional reliance upon NF-κB for the long-term survival of mature T cells. Together, these data indicate that the IKK-dependent survival of naïve CD4+ T cells depends on both repression of extrinsic cell death pathways and activation of an NF-κB-dependent survival program.
Type: | Article |
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Title: | IKK promotes naïve T cell survival by repressing RIPK1-dependent apoptosis and activating NF-κB |
Location: | United States |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1126/scisignal.abo4094 |
Publisher version: | https://doi.org/10.1126/scisignal.abo4094 |
Language: | English |
Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | Animals, Apoptosis, Cell Survival, I-kappa B Kinase, Mice, NF-kappa B, T-Lymphocytes |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
URI: | https://discovery.ucl.ac.uk/id/eprint/10173653 |
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