PMID- 37368952
OWN - NLM
STAT- MEDLINE
DCOM- 20230630
LR  - 20230630
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 16
IP  - 791
DP  - 2023 Jun 27
TI  - IKK promotes naive T cell survival by repressing RIPK1-dependent apoptosis and 
      activating NF-kappaB.
PG  - eabo4094
LID - 10.1126/scisignal.abo4094 [doi]
AB  - The inhibitor of kappaB kinase (IKK) complex regulates the activation of the nuclear 
      factor kappaB (NF-kappaB) 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 naive 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-kappaB p65 subunit) in mature CD4(+) T cells also resulted in loss of 
      naive CD4(+) T cells and in reduced abundance of the interleukin-7 receptor 
      (IL-7R) encoded by the NF-kappaB target Il7r, revealing an additional reliance upon 
      NF-kappaB for the long-term survival of mature T cells. Together, these data indicate 
      that the IKK-dependent survival of naive CD4(+) T cells depends on both 
      repression of extrinsic cell death pathways and activation of an NF-kappaB-dependent 
      survival program.
FAU - Carty, Fiona
AU  - Carty F
AD  - Institute of Immunity and Transplantation, Division of Infection and Immunity, 
      University College London, Royal Free Hospital, London NW3 2PP, UK.
FAU - Layzell, Scott
AU  - Layzell S
AD  - Institute of Immunity and Transplantation, Division of Infection and Immunity, 
      University College London, Royal Free Hospital, London NW3 2PP, UK.
FAU - Barbarulo, Alessandro
AU  - Barbarulo A
AD  - Institute of Immunity and Transplantation, Division of Infection and Immunity, 
      University College London, Royal Free Hospital, London NW3 2PP, UK.
FAU - Islam, Farjana
AU  - Islam F
AD  - Institute of Immunity and Transplantation, Division of Infection and Immunity, 
      University College London, Royal Free Hospital, London NW3 2PP, UK.
FAU - Webb, Louise V
AU  - Webb LV
AUID- ORCID: 0009-0000-8862-0199
AD  - Institute of Immunity and Transplantation, Division of Infection and Immunity, 
      University College London, Royal Free Hospital, London NW3 2PP, UK.
FAU - Seddon, Benedict
AU  - Seddon B
AD  - Institute of Immunity and Transplantation, Division of Infection and Immunity, 
      University College London, Royal Free Hospital, London NW3 2PP, UK.
LA  - eng
GR  - MR/P011225/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/N013867/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230627
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.1 (Ripk1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Apoptosis/genetics
MH  - Cell Survival/genetics
MH  - *I-kappa B Kinase/genetics/metabolism
MH  - *NF-kappa B/genetics/metabolism
MH  - T-Lymphocytes/metabolism
EDAT- 2023/06/27 19:13
MHDA- 2023/06/29 06:42
CRDT- 2023/06/27 14:02
PHST- 2023/06/29 06:42 [medline]
PHST- 2023/06/27 19:13 [pubmed]
PHST- 2023/06/27 14:02 [entrez]
AID - 10.1126/scisignal.abo4094 [doi]
PST - ppublish
SO  - Sci Signal. 2023 Jun 27;16(791):eabo4094. doi: 10.1126/scisignal.abo4094. Epub 
      2023 Jun 27.