The next chapter of apoptosis research

Recruiting the Immune System

Cells undergoing apoptosis (programmed cell death)

An exciting development in this field is the link between apoptosis and the immune system. The immune system is not activated in apoptosis which is a good thing as it results in the cell being disposed of without damaging surrounding cells. This is the major difference between programmed cell death and other types of cell death. Previously, it was thought that apoptotic cells were ignored by the immune system but recently this has been proven to be quite the opposite. “It looks like apoptotic cells are actively soliciting the help of the immune system to clear them and quite possibly also shutting down the aggressive microbe killing properties of the immune system”.

The ability for cells undergoing apoptosis to harness the immune system’s wound healing response is an exciting development and has implications for a new set of diseases. Harmful inflammation is associated with diseases such as rheumatoid arthritis and Crohn’s disease. “It seems that apoptosis may harness this wound healing response quite actively and that’s quite exciting because that may give us clues as to how we might use this information to manipulate the immune system in disease situations to harness a wound healing response and shut down the more inflammatory aggressive response”.

Martin published a paper a few years ago linking one of the proteins I mentioned earlier, caspases, to this immune system response. Caspases are involved in coordinating the demolition of the cell once programmed cell death has been activated. They are a key component in programmed cell death as they are “systematically shutting down the weapons at the cells disposal that could, if leaked out, activate the immune system”. Martin and his team showed that caspases inactivate a protein to prevent this immune response. The appropriately named protein, alarmin (or interleukin-33), is similar to a monitored alarm as when it’s turned on, the immune system police come with sirens blazing. Once caspases make a snip in its structure, it can no longer signal for help.

Linking Science & Industry

More recently, Martin’s lab have worked on another protein, interleukin-1 beta (IL1B), which acts in a similar way to alarmin. They discovered that “cell death related proteases trim off four amino acids from that protein to not only inactivate the protein but convert it to an antagonist to its own receptor”. Linking research and industrial application in a way that would make Science Foundation Ireland proud, they have patented this modified IL1B protein. This potential biopharmaceutical can prevent the production of the immune system recruiter IL1B. It may have applications in diseases such as rheumatoid arthritis and Crohn’s disease by reducing the harmful immune system response that underpins them. They are currently in talks with companies willing to take it to the clinical trial stage.

After chatting to Prof. Martin, I am even more fascinated by death of this kind. Now that the basic mechanisms are known, this field of research is becoming even more exciting. The hard work is beginning to pay off as science-based treatments are in various stages of development. An exciting chapter for apoptosis research!

Images: Courtesy of US National Library of Medicine (title) and the Molecular Cell Biology Lab, Trinity College Dublin (contents)

Lüthi AU, Cullen SP, McNeela EA, Duriez PJ, Afonina IS, Sheridan C, Brumatti G, Taylor RC, Kersse K, Vandenabeele P, Lavelle EC, & Martin SJ (2009). Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity, 31 (1), 84-98 PMID: 19559631

Martin SJ (2010). Cell biology. Opening the cellular poison cabinet. Science (New York, N.Y.), 330 (6009), 1330-1 PMID: 21127237

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