Faulty immune cells may play role in alopecia, other forms of baldness.
In experiments in mice, UC San Francisco researchers have discovered that regulatory T cells (Tregs), a type of immune cell generally associated with controlling inflammation, directly trigger stem cells in the skin to promote healthy hair growth. Without these immune cells as partners, the researchers found, the stem cells cannot regenerate hair follicles, leading to baldness.

“Our hair follicles are constantly recycling: when a hair falls out, a portion of the hair follicle has to grow back,” said Michael Rosenblum, MD, PhD, an assistant professor of dermatology at UCSF and senior author on the new paper. “This has been thought to be an entirely stem cell–dependent process, but it turns out Tregs are essential. If you knock out this one immune cell type, hair just doesn’t grow.”

The new study, published online May 26 in the journal Cell, suggests that defects in Tregs could be responsible for alopecia areata, a common autoimmune disorder that causes hair loss, and could potentially play a role in other forms of baldness, including male pattern baldness, Rosenblum said. Since the same stem cells are responsible for helping heal the skin after injury, the study raises the possibility that Tregs may play a key role in wound repair as well. Normally Tregs act as peacekeepers and diplomats, informing the rest of the immune system of the difference between friend and foe. When Tregs don’t function properly, we may develop allergies to harmless substances like peanut protein or cat dander, or suffer from autoimmune disorders in which the immune system turns on the body’s own tissues.

Rosenblum, who is both an immunologist and a dermatologist, wanted to better understand the role of these resident immune cells in skin health. To do this, he and his team developed a technique for temporarily removing Tregs from the skin. But when they shaved patches of hair from these mice to make observations of the affected skin, they made a surprising discovery.

In the new research, led by UCSF postdoctoral fellow and first author Niwa Ali, PhD, several lines of evidence suggested that Tregs play a role in triggering hair follicle regeneration.

First, imaging experiments revealed that Tregs have a close relationship with the stem cells that reside within hair follicles and allow them to regenerate: the number of active Tregs clustering around follicle stem cells typically swells by three–fold as follicles enter the growth phase of their regular cycle of rest and regeneration. Also, removing Tregs from the skin blocked hair regrowth only if this was done within the first three days after shaving a patch of skin, when follicle regeneration would normally be activated. Getting rid of Tregs later on, once the regeneration had already begun, had no effect on hair regrowth.

Tregs’ role in triggering hair growth did not appear related to their normal ability to tamp down tissue inflammation, the researchers found. Instead, they discovered that Tregs trigger stem cell activation directly through a common cell–cell communication system known as the Notch pathway. First, the team demonstrated that Tregs in the skin express unusually high levels of a Notch signaling protein called Jagged 1 (Jag1), compared to Tregs elsewhere in the body. They then showed that removing Tregs from the skin significantly reduced Notch signaling in follicle stem cells, and that replacing Tregs with microscopic beads covered in Jag1 protein restored Notch signaling in the stem cells and successfully activated follicle regeneration.