Journal article
RIPK3 controls MAIT cell accumulation during development but not during infection
T Patton, Z Zhao, XY Lim, E Eddy, H Wang, AG Nelson, B Ennis, SBG Eckle, MNT Souter, TJ Pediongco, HF Koay, JG Zhang, TM Djajawi, C Louis, N Lalaoui, N Jacquelot, AM Lew, DG Pellicci, J McCluskey, Y Zhan Show all
Cell Death and Disease | Published : 2023
Abstract
Cell death mechanisms in T lymphocytes vary according to their developmental stage, cell subset and activation status. The cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are largely unknown. Here we report that MAIT cells express key necroptotic machinery; receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) protein, in abundance. Despite this, we discovered that the loss of RIPK3, but not necroptotic effector MLKL or apoptotic caspase-8, specifically increased MAIT cell abundance at steady-state in the thymus, spleen, liver and lungs, in a cell-intrinsic manner. In contrast, over the course ..
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Grants
Awarded by University of Queensland
Funding Acknowledgements
AcknowledgementsWe acknowledge the Wurundjeri people of the Kulin nation as the traditional owners and custodians of the land on which most of the work was performed. We would like to thank John Silke, James Murphy and Genentech, for providing us with Ripk3-/-, Ripk3-/-Casp8-/-, Mlkl-/- and Mlkl-/-Casp8-/- mice, which were critical to this work. We thank Manuela Hancock and the WEHI animal staff Lisa Reid, Marina Patsis, Tom Kitson, Edan Azzopardi, Rhiannon Crawley, and Rebekah Meeny for technical assistance. We thank the staff at the Walter and Eliza Hall Institute and Doherty Institute node of the Melbourne Cytometry Platform for technical assistance, instrument access and work performing FACS sorts. We thank the Walter and Eliza Hall Institute and Melbourne biological resource facilities for excellent technical assistance. We thank Prof. David Fairlie and Dr Jeffrey Mak (Institute for Molecular Bioscience, University of Queensland) for the provision of synthetic 5-OP-RU. The authors thank Prof. Dale Godfrey and Prof. Andreas Strasser for advice and critical review. This work was supported by a Discovery Project Grant (DP210101416) from the Australian Research Council (ARC) and National Health and Medical Research Council of Australia (NHMRC) grants (1105209, 1113293, 1120467, 1145788), NHMRC Independent Research Institutes Infrastructure Support Scheme grant (361646), The University of Melbourne MDHS Research Grant Support Scheme and Victorian State Government Operational Infrastructure Support grant. SE is supported by an NHMRC Investigator grant (1196881). KEL (FT19010266) is, and AJC (FT160100083) was funded by Future Fellowships from the ARC. AJC is supported by a Dame Kate Campbell Fellowship from the University of Melbourne and an NHMRC Investigator Grant (1193745).