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IKK promotes naïve T cell survival by repressing RIPK1-dependent apoptosis and activating NF-κB.
- Source :
- Science Signaling; 6/27/2023, Vol. 16 Issue 791, p1-12, 12p
- Publication Year :
- 2023
-
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<superscript>+</superscript> T cells also resulted in loss of naïve CD4<superscript>+</superscript> 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<superscript>+</superscript> T cells depends on both repression of extrinsic cell death pathways and activation of an NF-κB–dependent survival program. Editor's summary: Mouse thymocyte survival depends on the suppression of cell death by the inhibitor of κB (IKK) complex, which phosphorylates and inactivates the cell death–promoting kinase RIPK1. Using lineage-specific, conditional knockout mice, Carty et al. investigated the role of IKK in the survival of mature naïve T cells after they leave the thymus. In addition to inhibiting RIPK1-dependent cell death, IKK also activated NF-κB–dependent, pro-survival signaling, which depended on the cytokine receptor IL-7R. Together, these data indicate how cell death and NF-κB signaling pathways are modulated during cellular differentiation.–John F. Foley [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19450877
- Volume :
- 16
- Issue :
- 791
- Database :
- Complementary Index
- Journal :
- Science Signaling
- Publication Type :
- Academic Journal
- Accession number :
- 164588620
- Full Text :
- https://doi.org/10.1126/scisignal.abo4094