M-CSF and GM-CSF Regulation of STAT5 Activation and DNA Binding in Myeloid Cell Differentiation is Disrupted in Nonobese Diabetic Mice. (12th November 2008)

• Record Type: Journal Article
• Authors: Rumore-Maton, B.; Elf, J.; Belkin, N.; Stutevoss, B.; Seydel, F.; Garrigan, E.; Litherland, S. A.
• Other Names: Putterman Chaim Academic Editor.
• Is Part Of: Clinical & developmental immunology. Volume 2008(2008)
• Publication Date: 2008-11-12
• Subjects: Developmental immunology -- Periodicals; Clinical immunology -- Periodicals; Immune System -- immunology -- Periodicals; Immune System -- growth & development -- Periodicals; Immune System Diseases -- immunology -- Periodicals; 571.9638
• DOI: 10.1155/2008/769795
• Languages: English
• ISSNs: 1740-2522

Abstract

Abstract : Defects in macrophage colony-stimulating factor (M-CSF) signaling disrupt myeloid cell differentiation in nonobese diabetic (NOD) mice, blocking myeloid maturation into tolerogenic antigen-presenting cells (APCs). In the absence of M-CSF signaling, NOD myeloid cells have abnormally high granulocyte macrophage colony-stimulating factor (GM-CSF) expression, and as a result, persistent activation of signal transducer/activator of transcription 5 (STAT5). Persistent STAT5 phosphorylation found in NOD macrophages is not affected by inhibiting GM-CSF. However, STAT5 phosphorylation in NOD bone marrow cells is diminished if GM-CSF signaling is blocked. Moreover, if M-CSF signaling is inhibited, GM-CSF stimulation in vitro can promote STAT5 phosphorylation in nonautoimmune C57BL/6 mouse bone marrow cultures to levels seen in the NOD. These findings suggest that excessive GM-CSF production in the NOD bone marrow may interfere with the temporal sequence of GM-CSF and M-CSF signaling needed to mediate normal STAT5 function in myeloid cell differentiation gene regulation.