Why do so many questions about immunology and GM-CSF persist?

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), also known as Colony Stimulating Factor 2 (CSF2), is an important haematopoietic growth factor and immune modulator. 

Secreted by a range of immune cells from macrophages to T-cells, and by endothelial cells, chondrocytes and fibroblasts, in response to bacterial endotoxins and inflammatory cytokines, such as IL-1 and IL-6, GM-CSF is a heavily glycosylated protein. This cytokine acts on haematopoietic stem cells to induce differentiation into both the granulocyte (neutrophils, eosinophils and basophils) and monocyte lineages. The induced differentiation of HSCs thus increases the number of circulating white cells to raise an immune response and protect the body against invasion or infection by microorganisms.
As a result of its immune system stimulating effects GM-CSF has recently been explored for use as an adjuvant for vaccines to increase both dendritic cell maturation and function and macrophage activity. It is currently used medically to stimulate white blood cells to prevent neutropenia following chemotherapy, in AIDS patients during therapy and following bone marrow transplantation. However, the side effects associated with its use in mobilising stem cells to raise the immune profile of patients often mean that alternative cytokines may be used either alone or in combination.
In autoimmune conditions like rheumatoid arthritis, where the immune system overreacts to the body’s own signals causing the immune system to attach and destroy healthy tissue, high levels of GM-CSF have been identified. Moreover, cancer-associated inflammation has also been linked to GM-CSF. This has led to research into potential antagonists of GM-CSF, with the hope that blocking the activity of this cytokine may inhibit the inflammation associated with these diseases.
Many examples exist of the importance of GM-CSF in basic biology and disease states and though we know it can be made by many cell types, we know very little about how production is regulated in these different cell types. We do not fully understand the factors which control the expression of GM-CSF receptors on cells or whether the different cells expressing this cytokine contribute to its differing functions in the development of different cell types of the immune system.