Interferon regulatory factor-8-driven myeloid differentiation is regulated by 12/15-lipoxygenase-mediated redox signaling.

Experimental Hematology
Michelle KinderEllen Puré

Abstract

Several transcription factors determine the cell fate decision between granulocytes and monocytes, but the upstream signal transduction pathways that govern myelopoiesis are largely unknown. Based on our observation of aberrant myeloid cell representation in hematopoietic tissues of 12/15-lipoxygenase (12/15-LOX)-deficient (Alox15) mice, we tested the hypothesis that polyunsaturated fatty acid metabolism regulates myelopoiesis. Multicolor flow cytometric analysis and methylcellulose assays were used to compare myelopoiesis and the differentiative capacity of progenitors from Alox15 and wild-type mice. Furthermore, we elucidated the mechanism by which 12/15-LOX is involved in regulation of myelopoiesis. Granulopoiesis in Alox15 mice is increased while monopoiesis is reduced. Moreover, there is an accumulation of granulocyte-macrophage progenitors that exhibit defective differentiation. Mechanistically, we demonstrate that transcriptional activity of interferon regulatory factor-8 (Irf8), which regulates myelopoiesis, is impaired in Alox15 progenitors and bone marrow-derived macrophages due to loss of 12/15-LOX-mediated redox regulation of Irf8 nuclear accumulation. Restoration of redox signaling in Alox15 bone marrow cells and g...Continue Reading

Citations

Mar 26, 2013·Cellular and Molecular Life Sciences : CMLS·René HuberKorbinian Brand
Aug 25, 2015·Redox Biology·Ryuichi Mashima, Torayuki Okuyama
Jun 26, 2012·Blood·Philip R TaylorValerie B O'Donnell
Feb 28, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joseph J MackelChad Steele
Feb 28, 2017·Wellcome Open Research·Sarah N LauderValerie O'Donnell
Jun 3, 2021·Biomolecules·Abhishek KulkarniIsabel Casimiro

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