| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610; and
Department of Microbiology, College of Medicine, University of Virginia, Charlottesville, VA 22908
Unstimulated monocytes of at-risk/type 1 diabetic humans and macrophages of the NOD mouse have markedly elevated autocrine GM-CSF production and persistent STAT5 phosphorylation. We analyzed the relationship between GM-CSF production and persistent STAT5 phosphorylation in NOD macrophages using reciprocal congenic mouse strains containing either diabetes-susceptible NOD (B6.NODC11), or diabetes-resistant C57L (NOD.LC11) loci on chromosome 11. These intervals contain the gene for GM-CSF (Csf2; 53.8 Mb) and those for STAT3, STAT5A, and STAT5B (Stat3, Stat5a, and Stat5b; 100.4–100.6 Mb). High GM-CSF production and persistent STAT5 phosphorylation in unactivated NOD macrophages can be linked to a region (44.9–55.7 Mb) containing the Csf2 gene, but not the Stat3/5a/5b genes. This locus, provisionally called Idd4.3, is upstream of the previously described Idd4.1 and Idd4.2 loci. Idd4.3 encodes an abundance of cytokine genes that use STAT5 in their macrophage activation signaling and contributes 
50% of the NOD.LC11 resistance to diabetes.
This article has been cited by other articles:
|
|
 |
|
  E. H. Leiter, P. C. Reifsnyder, R. Wallace, R. Li, B. King, and G. C. Churchill NOD x 129.H2g7 Backcross Delineates 129S1/SvImJ-Derived Genomic Regions Modulating Type 1 Diabetes Development in Mice Diabetes, July 1, 2009; 58(7): 1700 - 1703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. D. Dai, I. G. Marrero, P. Gros, H. Zaghouani, L. S. Wicker, and E. E. Sercarz Slc11a1 Enhances the Autoimmune Diabetogenic T-Cell Response by Altering Processing and Presentation of Pancreatic Islet Antigens Diabetes, January 1, 2009; 58(1): 156 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Litherland Immunopathogenic Interaction of Environmental Triggers and Genetic Susceptibility in Diabetes: Is Epigenetics the Missing Link? Diabetes, December 1, 2008; 57(12): 3184 - 3186. [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Marleau, K. L. Summers, and B. Singh Differential Contributions of APC Subsets to T Cell Activation in Nonobese Diabetic Mice J. Immunol., April 15, 2008; 180(8): 5235 - 5249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. McDuffie, N. A. Maybee, S. R. Keller, B. K. Stevens, J. C. Garmey, M. A. Morris, E. Kropf, C. Rival, K. Ma, J. D. Carter, et al. Nonobese Diabetic (NOD) Mice Congenic for a Targeted Deletion of 12/15-Lipoxygenase Are Protected From Autoimmune Diabetes Diabetes, January 1, 2008; 57(1): 199 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Enzler, S. Gillessen, M. Dougan, J. P. Allison, D. Neuberg, D. A. Oble, M. Mihm, and G. Dranoff Functional deficiencies of granulocyte-macrophage colony stimulating factor and interleukin-3 contribute to insulitis and destruction of {beta} cells Blood, August 1, 2007; 110(3): 954 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Brusko, C. Wasserfall, K. McGrail, R. Schatz, H. L. Viener, D. Schatz, M. Haller, J. Rockell, P. Gottlieb, M. Clare-Salzler, et al. No Alterations in the Frequency of FOXP3+ Regulatory T-Cells in Type 1 Diabetes Diabetes, March 1, 2007; 56(3): 604 - 612. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
