The b common (bc) family of cytokines, receptors and ligands

Published on December 5, 2011 Updated on July 7, 2022   40 min

Other Talks in the Category: Immunology

0:00
My name is Angel Lopez and I'm here with my colleague, Dr. Timothy Hercus who's to talk about the Beta common family of cytokines. They are receptors and ligands. We are both in the Division of Human Immunology at the Center for Cancer Biology of SA Pathology in Adelaide, Australia.
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The Beta common is the shared receptor subunit of a family of cytokines is the common subunit of heterodimeric receptors that comprise an Alpha chain that binds specifically to the cognate ligands and Beta common which is, as I said is shared amongst the three receptors. The three receptors are those for granulocyte macrophage colony stimulating factor which we refer to as GM-CSF and two interleukins, interleukin 3 or IL-3 and interleukin 5 or IL-5. These cytokines engage the receptors and exert multiple overlapping and redundant biological functions. The function probably the most important one is the survival. This function is activated throughout. The life of a given cell. But these cytokines can also promote the proliferation of the early progenitor cells and making them divide. As they divide they also differentiate into the mature progeny of myeloid cells that we see in peripheral blood. Once in the blood these cells can still be activated further by GM-CSF, IL-3 or IL-5 in this case the cytokines causing activation of myeloid cells. In this way they can more readily and more effectively kill invading pathogens. They can also migrate to sites of inflammation where they are required to clear a given infection. Typically these cytokines display considerable functional redundancy so that survival, proliferation, differentiation and activation is mediated by the three cytokines. Each one of them can promote these four functions. Now although the cytokines are very effective in vitro and in vivo to promote the production of blood cells in particular myeloid cells. They don't seem to be critical for steady-state hemopoiesis. In other words, if these cytokines are eliminated one by one by gene technology approaches. They are knockouts for GM-CSF or for IL-3 or IL-5. There's no major disruption of steady-state hemopoiesis. Normal hemopoiesis proceed as normal, perhaps an exception is IL-5 where lack of IL-5 causes a significant decrease in the normal levels of eosinophils, it's a decrease of about 90 percent. But the other lineages such as neutrophils and monocytes, etc don't seem to be affected in a big way. Instead, the way we see these cytokines at the moment is as being important for reactive hemopoiesis. In other words, in response to an outside stimulus, an injury or an insult the cytokines are produced in the body and then the elevation in the blood and in the bone marrow it stimulates the production of myeloid cells to come up in the blood so that we can then see elevated number of neutrophils. That's neutrophilia an elevated number of monocytes and eosinophilia which is an elevated number of eosinophils. By the type of cell that is elevated will depend very much on the type of cytokine that is being produced. The best example is IL-5, where elevation of IL-5 will give rise to almost exclusively the number of eosinophils in peripheral blood. Now the fact that these cytokines have overlapping activities makes it easy to understand that they respond to a common receptor organization theme. In essence, the fact that Beta common is shared by the three receptors goes a long way to explain why the three cytokines can stimulate pretty much the same functions, the main difference being the type of cells that is stimulated in each case. This in turn depends on the particular receptor that is expressed on the cell surface. For example, eosinophils will express all three receptors IL-5, IL-3 and GM-CSF. However, other cell types like neutrophils will express only GM-CSF. In this case the production of GM-CSF will give rise to neutrophils and monocytes. But neutrophils do not respond well to IL-3 or IL-5.
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The b common (bc) family of cytokines, receptors and ligands

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