Pallbearer gene helps immune cells destroy dying cells
15 October
The innate immune system is a defence we are born with. It is our first means of protection against infection and helps to keep the body healthy by sweeping away dead cells. Unlike the protection provided by more complex parts of the immune system, like antibody production, cells of the innate immune system do not need to learn how to respond to invasion, they do it automatically.
In her most recent study, Dr Nathalie Franc of the MRC Cell Biology Unit at UCL (University College London) set out to find out more about the genetics of natural immune protection. To do this, she looked at cell death - when a healthy cell comes to the end of its useful life it begins to self-destruct, a process known as apoptosis. To understand more about how genetics influence cell death, Dr Franc and her team used fruit flies to look for the genes required for dying cells to be efficiently consumed by their neighbours or patrolling immune system cells, the crucial end point of apoptosis.
The process of cleaning up dead cells is called phagocytosis. It is most often performed by patrolling white blood cells – macrophages - that belong to the innate immune system. The macrophages engulf a dead cell by stretching their membrane around it, creating a pocket to hold the cell and then attacking it with proteins that cause the whole cell to break into its original constituent parts. The leftovers are then released; when this happens near the surface of the skin the remnants create pus.
The team discovered that a gene named pallbearer or pall plays a role in facilitating efficient removal of suicidal cells. Pallbearer joins at least three proteins that modify and target one or several specific proteins for destruction. This results in the efficient clearance of dying cells. The results are published online in the journal Immunity.
Commenting on the significance of her discovery Dr Franc said: ‘‘Understanding what triggers and facilitates dying cell engulfment by a macrophage will help us to learn more about our most simple form of defence: innate immunity. The process of cell death is essential to the development of tissues and organs, and a crucial part of the healthy cell cycle.”
“The next important step is for us to identify the protein or proteins that are modified by the Pallbearer complex, characterize their molecular function and thus understand how their degradation leads to efficient removal of dying cells. Patients with autoimmune diseases, such as Lupus - Systemic Lupus Erythematosus [SLE], have within their inflamed tissues an elevated level of dead cells that are not being efficiently cleared, which contributes to their condition or its worsening.”
“Our work is still at a basic research stage, but it is our hope that by continuing to decipher the molecular mechanisms underlying the destruction of dying cells by macrophages, which are conserved in humans, we may provide some much needed clues to allow for the design of drugs that may help patients with autoimmune diseases boost their natural defence against self-destruction.”
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