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IKK promotes naïve T cell survival by repressing RIPK1-dependent apoptosis and activating NF-κB

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. Green open access

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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
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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