Blood: MiR-146a deficiency links IL6/TNFD induced inflammation to myelin malignancies

Aging is associated with significant changes in the hematopoietic system, including increased inflammation, impaired function of hematopoietic stem cells (HSC) and increased incidence of myelin malignanciesInflammation of aging is thought to be a driver of age-related changes in HSC function and myelin malignancy, but the mechanisms of these phenomena remain unclearGrants and others have found that the absence of miR-146a in AML patients is a cause of aging-related inflammationIn older wild mice, the expression of miR-146a decreased, and in young mice with miR-146a deficiency, the absence of miR-146a promoted early aging and inflammation of HSC, and early onset of myelin malignancies associated with agingThe resting, dry, differentiation potential and epigenetic state of HSC were determined by single-cell method to explore the function and group structure of HSC, and the absence of miR-146a was found to exhaust the original, stationary HSCs subgroupDNA methylation and transcription group spectrum suggest nf-B, IL-6, and TNF as potential drivers of HSC dysfunction, activate inflammatory signal transduction, and promote mature miR-146a-/-myelin and lymphocyte secretion OF IL6 and TNFReducing inflammation by targeting Il6 or Tnf is sufficient to restore the single-cell function and subgroup structure of miR-146a-/HSC and reduce the incidence of blood malignancies in miR-146a-/-miceThe increased sensitivity of miR-146a-/-HSCs to IL6 stimulation suggests that miR-146a deficiency can affect HSC function through extracellular inflammatory signals and increased intracellular inflammatory sensitivityTherefore, miR-146a is missing to regulate the internal and external source mechanism of cells, linking HSC inflammation with the development of bone marrow malignancies