An early regulatory mechanism of hyperinflammation by restricting monocyte contribution
July 8, 2024
Abstract
Innate immune cells play a key role in inflammation as a source of pro-inflammatory cytokines. However, it remains unclear how innate immunity-mediated inflammation is fine-tuned to minimize tissue damage and assure the host’s survival at the early phase of systemic inflammation. The results of this study with mouse models demonstrate that the supply of monocytes is restricted depending on the magnitude of inflammation. During the acute phase of severe inflammation, monocytes, but not neutrophils, were substantially reduced by apoptosis and the remaining monocytes were dysfunctional in the bone marrow. Monocyte-specific ablation of Casp3/7 prevented monocyte apoptosis but promoted monocyte necrosis in the bone marrow, leading to elevated levels of pro-inflammatory cytokines and the increased mortality of mice during systemic inflammation. Importantly, the limitation of monocyte supply was dependent on pro-inflammatory cytokines in vivo. Consistently, a reduction of monocytes was observed in the peripheral blood during cytokine-release syndrome (CRS) patients, a pathogen-unrelated systemic inflammation induced by chimeric antigen receptor-T cell (CAR-T cell) therapy. Thus, monocytes act as a safety valve to alleviate tissue damage caused by inflammation and ensure host survival, which may be responsible for a primitive immune-control mechanism that does not require intervention by acquired immunity.
Journal Article
JOURNAL： Frontiers in Immunology
TITLE： An early regulatory mechanism of hyperinflammation by restricting monocyte contribution
DOI： https://doi.org/10.3389/fimmu.2024.1398153
TITLE： An early regulatory mechanism of hyperinflammation by restricting monocyte contribution
DOI： https://doi.org/10.3389/fimmu.2024.1398153
Correspondence to
Toshiaki Ohteki, Professor
Department of Biodefense Research,
Medical Research Institute,
Tokyo Medical and Dental University(TMDU)
E-mail:ohteki.bre（at）mri.tmd.ac.jp
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