Granulocyte macrophage-colony stimulating factor (GM-CSF) recruits immune cells to the pancreas and delays STZ-induced diabetes.
Granulocyte macrophage-colony stimulating factor (GM-CSF) is one of the most widely used growth factors for enhancing immune responses and is known to recruit and activate antigen-presenting cells (APCs). This study hypothesized that overexpression of this cytokine within the pancreatic beta-cells would recruit, expand, and activate APCs. The question was whether this would lead to tolerance or autoimmunity to pancreatic antigens. This possibility was tested by preparing transgenic mice (ins-GM-CSF) whose islets expressed murine GM-CSF. By 6-8 weeks of age, these mice developed a profound mononuclear cell infiltration that often overwhelmed the exocrine pancreas, although no changes in enzyme or hormone function were apparent. The majority of the mononuclear infiltrate within the pancreas was identified as F4/80+ macrophages. Transgenic ins-GM-CSF mice had splenomegaly due to a massive increase in the macrophage population. Additionally, mononuclear cells were found within the livers of transgenic mice, with F4/80+ cells also identified within the infiltrate, indicating that GM-CSF-activated mononuclear cells circulated to organs other than the pancreas. To assess the disease potential, this study tested whether macrophage recruitment to the pancreas might accelerate or protect the islets from diabetes. It was found that the induction of diabetes by low-dose streptozotocin (STZ) was delayed and reduced within ins-GM-CSF transgenic mice, in comparison with negative littermates. Together, these data highlight the role of GM-CSF in recruiting APCs such as macrophages. Advanced cellular infiltration does not overtly harm, and may even protect, pancreatic function, as seen with the delay in chemically induced diabetes.
Krakowski
Michelle
M
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Abdelmalik
Robin
R
Mocnik
Lorraine
L
Krahl
Troy
T
Sarvetnick
Nora
N
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D004198:Disease Susceptibility; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology; D013163:Splenomegaly / Q000276:immunology
D016178:Granulocyte-Macrophage Colony-Stimulating Factor