How the 'Garbage Men' of Our Bodies Remove Dead Cells in Different Environments

We generate billions of dead cells every day. These cells are then removed by the trash collectors of our body, specialized immune cells; yet when these cells don't do their jobs, waste can pile up, destroy healthy tissue and lead to conditions like lupus and rheumatoid arthritis. Now, though, researchers are getting a closer look at this process and have found how two critical receptors on these trash-eating cells identify and engulf dead cells in different environments.

"To target these receptors as treatments for autoimmune disease and cancer, it's important to know exactly which receptor is going what," said Greg Lemke, one of the researchers, in a news release. "And this discovery tells us that."

The cells that dispose garbage are known as macrophages. They have wide arrays of receptors on their surface, two of which are called Mer and Axl; these two are responsible for recognizing dead cells in normal environments and inflamed environments, respectively.

Mer, Axl and another receptor make up the TAM family, which is a group of receptors that clear out "garbage" cells in our bodies. The absence of these receptors has dramatic effects on the immune system, including the development of autoimmune disease.

In this latest work, the scientists found multiple critical differences between Axl and Mer. The receptors use different molecules, called ligands, to be activated; Axl has a single such ligand and once engaged, is quickly cleaved off of the surface of the macrophage.

"We compared the behavior and regulation of the receptors and the results were very striking," said Anna Zagorska, first author of the new study, in a news release. "In response to many different pro-inflammatory stimuli, Axl was upregulated and Mer was not. In contrast, immunosuppressive croticosteroids, which are widely used to suppress inflammation in people, upregulated Mer and suppressed Axl. These differences were our entry point to the study."

The researchers also looked into each receptor's activity in more detail and found that the receptors are unusual in that they have a three-step binding procedure. This, in particular, may help scientists created more targeted therapies for cancers and other diseases in which these receptors are involved.

The findings are published in the journal Nature Immunology.