biostudies-literaturePatton TDepartment of Health | National Health and Medical Research Council (NHMRC)111https://www.ebi.ac.uk/biostudies/studies/S-EPMC9922319biostudies-literatureUnknown14(2)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 of infection with Francisella tularensis, RIPK3 deficiency did not impact the magnitude of the expanCell death & diseaseRIPK3 controls MAIT cell accumulation during development but not during infection.PMC9922319112046711457881113293119374511052091196881Zhang JGPediongco TJPatton TKoay HFJacquelot NLawlor KEWang HZhao ZMcCluskey JZhan YEnnis BNelson AGDjajawi TMEckle SBGChen ZEddy ELew AMLouis CLim XYLalaoui NSouter MNTPellicci DGCorbett AJfalseRIPK3 controls MAIT cell accumulation during development but not during infection.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 of infection with Francisella tularensis, RIPK3 deficiency did not impact the magnitude of the expan2023-01-01T00:00:00Z2023 Feb2025-04-18T20:04:24.937Z2025-04-07T07:50:43.545ZS-EPMC99223193677434210.1038/s41419-023-05619-0