Blanchett, Sam;
Dondelinger, Yves;
Barbarulo, Alessandro;
Bertrand, Mathieu JM;
Seddon, Benedict;
(2022)
Phosphorylation of RIPK1 serine 25 mediates IKK dependent control of extrinsic cell death in T cells.
Frontiers in Immunology
, 13
, Article 1067164. 10.3389/fimmu.2022.1067164.
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Abstract
The Inhibitor of Kappa B Kinase (IKK) complex is a critical regulator of NF-κB activation. More recently, IKK has also been shown to repress RIPK1 dependent extrinsic cell death pathways by directly phosphorylating RIPK1 at serine 25. In T cells, IKK expression is essential for normal development in the thymus, by promoting survival of thymocytes independently of NF-κB activation. RIPK1 undergoes extensive phosphorylation following TNF stimulation in T cells, though which targets are required to repress RIPK1 has not been defined. Here, we show that TNF induced phosphorylation of RIPK1 at S25 is IKK dependent. We test the relevance of this phosphorylation event in T cells using mice with a RIPK1S25D phosphomimetic point mutation to endogenous RIPK1. We find that this mutation protects T cells from TNF induced cell death when IKK activity is inhibited in vitro, and can rescues development of IKK deficient thymocytes in vivo to a degree comparable with kinase dead RIPK1D138N. Together, these data show that phosphorylation of RIPK1S25 by IKK represents a key regulatory event promoting survival of T cells by IKK.
Type: | Article |
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Title: | Phosphorylation of RIPK1 serine 25 mediates IKK dependent control of extrinsic cell death in T cells |
Location: | Switzerland |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.3389/fimmu.2022.1067164 |
Publisher version: | https://doi.org/10.3389/fimmu.2022.1067164 |
Language: | English |
Additional information: | © 2022 Blanchett, Dondelinger, Barbarulo, Bertrand and Seddon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | T cells, extrinsic cell death, RIPK1, IKK complex, TNF |
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/10162366 |
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