November 15, 2018

Straightforward. Clear. Innovative.

These words aptly describe the research that Jillian Richmond, PhD, of the University of Massachusetts Medical School at Worcester, MA, is conducting with a grant from the Lupus Research Alliance.

She is looking for ways to stop lupus from damaging healthy tissue. But to attain a better picture of Dr. Richmond’s investigation, we just need one more word: Promising.

Building on her vast experience in the field of autoimmune skin Dr. Jillian Richmond diseases, Dr. Richmond is seeking to understand the pathology of cutaneous lupus erythematosus (CLE). Her goal: better diagnostics and new treatment targets for both skin-limited and systemic lupus.

She started with a very basic — but critical — question: What drives white blood cells to travel around the body?

Dr. Richmond explains: “Pertinent to both infection and to autoimmune diseases are proteins the body expresses that tell cells where to go. So if someone cuts himself, there are proteins that will say to his white blood cells, ‘Hey there’s a cut and you need to come clear out any infection and start the healing process’ — but in lupus, those signals can get turned on inappropriately.”

Dr. Richmond and her team have found specific proteins highly expressed in the skin that are required for getting white blood cells there, and they are prominent in lupus.

Here’s what’s going on at the molecular level: CXCL9 and CXCL10 are protein ligands — or chemoattractants — that are made in the skin and bind to CXCR3 on white blood cells in order to direct the cells into the tissue where they can wreak havoc.

Dr. Richmond helps her students to understand this complex process by asking them to imagine finding a bottle of perfume when they are blindfolded. “In this example, your nose is CXCR3 and the perfume is CXCL9 and 10. Following the scent to the strongest area is how the cells find their way into the skin tissue,” she explains. “So it is highest at the site of injury or, in the case of lupus, the site of disease activity. And that is how the cells are finding their way there.”

The next step for Dr. Richmond is to understand the functional significance of her findings in murine models and, eventually, to find a way to disrupt the course of lupus by blocking CXCR3 or its ligands.