July 31: Your body depends on T cells to stay healthy. These white blood cells act like a neighborhood watch in the body, helping the immune system spot threats such as viruses, bacteria, and cancer cells. When danger appears, they sound the alarm and help coordinate an immune response. Some T cells can even destroy infected or cancerous cells directly.
For more than 20 years, Jillian Richmond, Ph.D., an assistant professor of comparative pathobiology at Cummings School of Veterinary Medicine at Tufts University, has studied what happens when T cells fall out of balance.
“I look at the yin and yang of T cells,” she said. “If T cells are not doing their job, we can develop tumors. But if they are overactive, T cells can start attacking healthy tissues in the body. My work focuses on understanding how we can boost T cell activity in anti-tumor responses, but also how to turn that down in autoimmune diseases.”
Richmond discussed how her research could lead to better treatments for skin diseases in both people and pets.
How did a T cell biologist become interested in studying skin disease?
As a T cell biologist, immunology is what first drew me to the skin. Humans and other primates actually have about twice as many T cells in their skin as in their blood. That makes sense when you think about it: The skin is the body’s first line of contact with the outside world, where it regularly encounters viruses, bacteria, fungi, and other potential threats.
A lot of people think of skin disorders as more of a cosmetic issue. However, skin health impacts the health of the whole body. It’s your biggest organ and has significant immune functions. It serves as a barrier to the outside world.
Why are you looking at skin disorders in pet dogs as well as people?
Dogs develop a version of lupus that closely resembles discoid lupus erythematosus in people. Lupus is an autoimmune disease in which the immune system mistakenly attacks healthy tissues. In both dogs and humans, T cells drive much of that damage by attacking skin cells and hair follicles.
The disease can have a major impact on quality of life. Both people and dogs with lupus are highly sensitive to sunlight. Sun exposure can trigger scaly, raised rashes that may eventually lead to permanent scarring, hair loss, and changes in skin color. Severe skin inflammation can also worsen disease elsewhere in the body, including the kidneys.
Because dogs have so much hair-bearing skin, they provide an especially useful way to investigate what happens inside the hair follicle to develop better treatments for lupus.
What have you learned so far?
Before I joined Cummings School as an assistant professor last year, I taught there part-time, collaborating with veterinary dermatologist Ramón Almela, D.V.M., Ph.D., DECVD, while leading a research team at UMass Chan Medical School.
We identified inflammatory pathways that represent promising treatment targets for canine lupus. Drugs that block these pathways—called JAK inhibitors—are already being tested or used for other conditions such as skin allergies, raising the possibility that they could be repurposed to treat discoid lupus. A pilot study was recently completed using JAK inhibitors for canine discoid lupus, and it worked! It was really exciting to see our preclinical work influencing drug repurposing.
To better understand how T cells cause discoid lupus, we recently collaborated with researchers Cheri Frey, M.D. and Angel Byrd, M.D. Ph.D. at Howard University College of Medicine to closely examine hair follicles and the immune cells around them in skin samples from pet dogs and people with discoid lupususing spatial sequencing.
One of the things we discovered is that hair follicles appear to release chemical signals that act like distress beacons, drawing T cells into the follicle. Once there, those cells can trigger inflammation and tissue damage. We found that the same signaling pathways were active in both canine and human lupus, which reinforces the idea that dogs can serve as an important model for understanding the disease. We are now working on next generation therapies for discoid lupus in pet dogs and peopleto hopefully improve safety and efficacy.
What’s next for your lupus research at Cummings School?
In collaboration with Qi Tang, Ph.D., an RNA chemist at UMass, we’re testing a new type of therapy that uses small, specially designed molecules to “silence” a specific JAK gene involved in driving inflammation in lupus. This approach has already shown promise in other preclinical studies and is now being tested in early human trials for a different type of hair loss condition. We’ve adapted it for dogs, since even small genetic differences between species matter.
Now we are conducting a clinical trial in pet dogs being treated for discoid lupus at Henry and Lois Foster Hospital for Small Animals. Supported by the Lupus Research Alliance, the study will test whether a single, targeted injection into affected skin can calm inflammation in the long term. We’re also comparing it to another common inflammatory skin disease, called atopic dermatitis, to better understand how broadly the treatment might work.
One of the advantages of this approach is that it is highly localized. Instead of giving a daily medication that affects the whole body, the treatment is injected directly into the skin, where the disease is active. That could mean fewer side effects and longer-lasting relief for pets—and potentially someday for people as well.
Your work focuses on both autoimmune disease and cancer. How are you applying what you’ve learned about T cells to treat skin cancers in dogs?
One of the other diseases we’re studying is cutaneous T-cell lymphoma, a type of skin cancer that develops in dogs and people when T cells themselves become malignant. It’s an interesting contrast to lupus. In lupus, we’re trying to calm down overactive T cells that are attacking healthy tissue. In cutaneous T-cell lymphoma, the challenge is either eliminating the cancerous T cells or helping healthy T cells recognize and destroy them.
Some forms of the disease are particularly aggressive in both species and can be difficult to treat. Because cutaneous T cell lymphoma is relatively rare in humans, it can be difficult to test new therapies. One of our goals is to study naturally occurring disease in pet dogs to identify promising treatment strategies that could benefit veterinary patients while also informing future clinical trials in people.
Cheryl London, D.V.M., Ph.D., DACVIM, V90, associate dean for research and Anne Engen and Dusty Professor in Comparative Oncology at Cummings School, and I are exploring combinations of immunotherapies and targeted drugs, including JAK inhibitors, which can interfere with signals that cancerous T cells use to survive and multiply. In some dogs enrolled in our previously completed pilot studies at the Foster Hospital, we saw encouraging responses when these treatments were added after other therapies stopped working.
