Clearing dead cells is a vital part of the body’s functioning. Cells that are aging, damaged or infected are programmed to die, a process called apoptosis, then cleared out and replaced. The clearance is carried out by immune cells called phagocytes which engulf and destroy the apoptotic cells.
“If a dying cell is not cleared it will go into a post-apoptotic stage called necrosis, where it will lose its membrane permeability and spill its intracellular components into the periphery,” explained Terry Means, an assistant professor of medicine at Harvard Medical School, in an email to this Correspondent. Dr. Means is the corresponding author of a paper published in Nature recently. “These intracellular components have never been seen by our immune system and often an antibody response is generated against them.”
This is commonly seen in several inflammatory diseases like lupus in humans. The team led by Means has described a molecule that is crucial for dead cell removal in mice and, if confirmed in humans, could be used to treat such disorders.
Dead cells differentiate themselves from their healthy counterparts by molecules on their surface that act as “eat me” signals for phagocytes. C1q molecule is one such “eat me” signal. What was not known until now is the receptor protein on the phagocyte which recognises and binds to the C1q on the dead cell, before engulfing it.
In the C. elegans worm, a receptor called CED-1 is known to do this. Mice and humans have a similar protein called SCARF1 on the surface of their phagocytes. The scientists wanted to test the hypothesis that SCARF1 in mammals could be playing a similar role as CED-1 in worms.
For this, Means and his team bred mice modified to lack SCARF1. They found that dead cell clearance in these mice was impaired and within a few months they developed lupus-like symptoms. This proved that the receptor is indeed crucial to recognise and engulf dead cells with the C1q “eat me” signal. The SCARF1-mediated mechanism is not the only mode of dead cell clearance, but it is a significant one. “Based upon our studies we believe that SCARF1 controls approximately 40 per cent of dead cell clearance,” said Means.
According to Means human SCARF1 too has been shown to mediate binding and engulfment of C1q-bound dead cells, but that’s not enough. “Further work will be needed to inhibit SCARF1 expression on human cells or to identify humans with SCARF1 deficiency to determine the role in humans.”
If SCARF1 proves to play a role in humans, then treatment strategies involving drugs that increase SCARF1 expression, or SCARF1 proteins that enhance the uptake of dead cells could be designed for lupus patients.