Justine E Roderick-Richardson, Sung-Eun Lim, Sakiko Suzuki, Mohd Hafiz Ahmad, Jonathan Selway, Reem Suleiman, Keshab Karna, Jesse Lehman, Joanne O'Donnell, Lucio H Castilla, Jonathan Maelfait, Jan Rehwinkel, Michelle A Kelliher
Human bone marrow failure (BMF) syndromes result from the loss of hematopoietic stem and progenitor cells (HSPC), and this loss has been attributed to cell death; however, the cell death triggers, and mechanisms remain unknown. During BMF, tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ) increase. These ligands are known to induce necroptosis, an inflammatory form of cell death mediated by RIPK1, RIPK3, and MLKL. We previously discovered that mice with a hematopoietic RIPK1 deficiency ( Ripk1 HEM KO ) exhibit inflammation, HSPC loss, and BMF, which is partially ameliorated by a RIPK3 deficiency; however, whether RIPK3 exerts its effects through its function in mediating necroptosis or other forms of cell death remains unclear...
January 23, 2024: Proceedings of the National Academy of Sciences of the United States of America