Iron is Needed to Help Produce Dendritic Cells

Byron's Comments:

Dendritic cells need iron for health and don't work well when iron is not adequate during their formation.

Study Title:

Differentiation of functional dendritic cells and macrophages from human peripheral blood monocyte precursors is dependent on expression of p21 (WAF1/CIP1) and requires iron.

Study Abstract:

Iron is required for monocyte/macrophage differentiation of HL-60 leukaemia cells. Differentiation requires induction of the cyclin-dependent kinase inhibitor p21 (WAF1/CIP1), and cell cycle arrest at the G1/S checkpoint. With iron depletion, p21 induction and differentiation are blocked. To establish the roles of iron and p21 in normal monocyte/macrophage differentiation, we examined generation of dendritic cells (DCs) and macrophages from peripheral monocytes. Monocytes were cultured with interleukin 4 and granulocyte-macrophage colony-stimulating factor (GM-CSF), then treated with lipopolysaccharide to produce DCs or with M-CSF to produce macrophages. Iron deprivation was induced by desferrioxamine (DF). Monocyte-derived DCs had characteristic phenotype and morphology, and stimulated proliferation of naïve allogeneic T lymphocytes. In contrast, DCs generated under iron deprivation were phenotypically undifferentiated and did not stimulate T cells. Similarly, macrophages expressed a characteristic phenotype and morphology, and phagocytosed latex beads, but macrophages generated under iron deprivation failed to develop a mature phenotype and had impaired phagocytosis. Iron deprivation blocked induction of p21 (WAF1/CIP1) expression in both DC and macrophage cultures. Furthermore, p21 antisense oligonucleotides, but not sense oligonucleotides, inhibited both DC and macrophage differentiation. These data indicate that a key role of iron in haematopoiesis is to support induction of p21 which, in turn, is required for DC and macrophage differentiation.

Study Information:

Kramer JL, Baltathakis I, Alcantara OS, Boldt DH. Differentiation of functional dendritic cells and macrophages from human peripheral blood monocyte precursors is dependent on expression of p21 (WAF1/CIP1) and requires iron. Br J Haematol.  2002 June 117(3):727-34.
Department of Medicine/Hematology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.



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