Blocking CXCR7 Receptor of Mature Monocytes Could Be New Therapeutic Strategy in MS

The CXCR7 receptor present on mature monocytes — a type of white blood cell — may be a therapeutic target to alleviate the inflammation seen in multiple sclerosis (MS) and similar disorders, a new study shows.

The study, “Frontline Science: CXCR7 mediates CD14⁺CD16⁺ monocyte transmigration across the blood brain barrier: a potential therapeutic target for NeuroAIDS,” appeared in the Journal of Leukocyte Biology.

“Migration of blood monocytes to the brain can be involved in many diseases, including autoimmunity and spread of infections like HIV to the brain,” said John Wherry, deputy editor of the Journal of Leukocyte Biology. “These new findings might provide a novel approach to prevent these ‘Trojan horses’ in the cases of HIV from transporting their payload to the brain.”

Mature monocytes, also known as CD14⁺CD16⁺ monocytes, comprise 5 to 10 percent of all monocytes. They migrate into the central nervous system (CNS) in response to molecules called chemokines. Once there, they trigger several processes that can cause neuron damage and neuroinflammation. These monocytes have been known to migrate in many diseases including MS and HIV infection.

CXCR7 is found on different types of monocytes, and responds to the chemokine CXCL12, which is higher in people with neurological disease.

Multiple studies have tried to determine the presence of CXCR7 on the surface of mature monocytes with varying results. If CXCR7 is restricted to only being expressed on the surface of mature monocytes, that could indicate a potential therapeutic target. That led researchers to try to determine CXCR7’s role in the migration of mature monocytes.

Mature monocytes are found to be very susceptible to infection by HIV, and have been found in the CNS of HIV-infected people. These cells are thought to actually facilitate the entry of HIV into the CNS. For this reason, researchers used HIV-infected mature monocytes to investigate the role of CXCR7.

First, researchers demonstrated that CXCR7 is present on mature monocytes from both HIV-infected and normal individuals, and that it indeed aisd the migration of mature monocytes across the blood-brain barrier by responding to CXCL12.

Then, researchers treated mature monocytes with the CXCR7 antagonist CCX771, which selectively inhibits the CXCR7-activated pathways. This led to a reduction in the migration of mature monocytes across the blood-brain barrier, and thus, entry into the brain.

“Since mature monocytes appear to be the only white blood cells that primarily use CXCR7 to respond to the CXCL12 brain stimulus, we may have hit upon a novel method to block inflammation and HIV infection in the brain,” Mike Veenstra, the study’s first author, said in a press release. Veenstra is a researcher at the Departments of Pathology, and Microbiology and Immunology, at Albert Einstein College of Medicine in Bronx, New York.

He added: “We propose that CXCR7 is a therapeutic target on CD14⁺CD16⁺ monocytes to limit their CNS entry, thereby reducing neuroinflammation, neuronal damage and HIV-associated neurocognitive disorders. Our data also suggest that CCX771 may reduce CD14⁺CD16⁺ monocyte-mediated inflammation in other disorders.”