After studying their activity in mice, researchers have discovered that a type of immune cell normally associated with inflammation, or regulatory T cells, also promote hair growth by triggering stem cells in the skin. Mice without these particular immune cells cannot regenerate hair. The researchers suggest that defects in regulatory T cells could be a cause of alopecia areata and may also contribute to other forms of baldness.
A report on the study - led by the University of California-San Francisco (UCSF) - is shortly to be published in the journal Cell.
Senior author Michael Rosenblum, an assistant professor of dermatology at UCSF, explains that hair follicles are continually regenerating. He says that "when a hair falls out, the whole hair follicle has to grow back."
Before this study, it was thought that stem cells were completely in charge of hair follicle recycling.
However, the new research reveals that regulatory T cells, commonly termed Tregs, are essential to hair follicle recycling. "If you knock out this one immune cell type," says Prof. Rosenblum, "hair just doesn't grow."
The team suggests that faulty Tregs may be behind alopecia areata - a common autoimmune disease that causes loss of hair on the scalp and other parts of the skin.
Although it most often begins in childhood, alopecia areata can arise in males and females of any age or race. It is thought to affect around 147 million people worldwide at some point in their lives, including around 6.8 million in the United States.
In alopecia areata, the hair follicles shrink and slow hair production. However, the follicles remain alive and can resume producing healthy hair again months or years later - even without treatment.
Tregs have a role outside of immune system
The researchers suggest that the discovery may also explain other forms of hair loss, such as male pattern baldness. They also propose that Tregs may play a role in wound healing, since that involves the same skin stem cells.
It was once thought that Tregs were only involved in inflammation and regulating immune tolerance, where they help to differentiate between harmless and harmful presences in the body.
Defects in Tregs give rise to diseases such as autoimmune disorders (in which the immune system attacks the body's own tissue) and allergies (in which a harmless agent - such as peanut protein - is identified as foe).
Tregs predominantly reside in the lymph nodes, along with other types of immune cell. However, in their paper, the researchers note that Tregs are increasingly being found in other tissues, where they carry out specialized functions that are unique to those tissues.
In previous work with mice, Prof. Rosenblum and his team had shown that Tregs help the skin of newborns develop immune tolerance and release molecules that assist with wound healing throughout the animals' lives.
The team was looking at other possible roles for Tregs in skin, when they made the surprising discovery about hair follicles.
Evidence of Tregs' role in hair regeneration
The new study yields several pieces of evidence about the role of Tregs in hair regeneration.
For example, in imaging experiments, the team found that during the growth phase of the hair follicle regeneration cycle, the number of active Tregs around the stem cells increases threefold.
In another experiment, the researchers found that depleting mouse skin of Tregs only prevents hair regeneration when performed within 3 days of shaving some skin off. If done after this, when follicle regeneration has already started, it has no effect.
The team also found that the hair growth function of Tregs is not related to their inflammation role. Hair regeneration signals are sent through a pathway called Notch that communicates directly with the hair follicle stem cells.
They found that compared with Tregs in other parts of the body, skin Tregs have high levels of Jag1, a Notch signaling protein. When they depleted Tregs in the skin, it significantly reduced Notch signaling in follicle stem cells, and when they replaced the Tregs with microscopic beads sporting Jag1 protein, it restored the signaling and prompted follicle regrowth.
Prof. Rosenblum says that their evidence supports the idea that Tregs coevolved with the stem cells, "so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work." He says that the stem cells appear to depend on the Tregs to tell them when to start the regrowth cycle. He concludes:
"We think of immune cells as coming into a tissue to fight infection, while stem cells are there to regenerate the tissue after it's damaged. But what we found here is that stem cells and immune cells have to work together to make regeneration possible."
He and his colleagues believe that their discovery will be important for alopecia areata research. They found that the genes associated with alopecia are almost all linked to Treg activity.