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Clinical and Developmental Immunology
Volume 2008, Article ID 769795, 8 pages
http://dx.doi.org/10.1155/2008/769795
Research Article

M-CSF and GM-CSF Regulation of STAT5 Activation and DNA Binding in Myeloid Cell Differentiation is Disrupted in Nonobese Diabetic Mice

1College of Veterinary Medicine, University of Florida, 2015 SW 16th Avenue, Gainesville, FL 32610, USA
2Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, P. O. BOX 100275, 1600 SW Archer Road, Gainesville, FL 32610, USA
3Burnham Institute for Medical Research-Lake Nona, SLSL Buliding M6-1025, Rm 102-9, Kennedy Space Center, Lake Nona, FL 32899, USA

Received 4 May 2008; Revised 13 August 2008; Accepted 23 October 2008

Academic Editor: Chaim Putterman

Copyright © 2008 B. Rumore-Maton et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.