Hair-raising research: La Jolla scientists find surprising link between immune system and hair growth

Ye Zheng (left) and Zhi Liu of the Salk Institute for Biological Studies
Ye Zheng (left) and Zhi Liu of the Salk Institute for Biological Studies in La Jolla describe in a new study how immune cells can help generate new hair follicles and hair growth.
(Courtesy of Salk Institute)

Scientists at the Salk Institute for Biological Studies in La Jolla say they have uncovered why a common treatment for alopecia — a condition in which the immune system attacks a person’s own hair follicles, causing hair loss — is so effective.

The findings, published June 23 in Nature Immunology, describe how immune cells called regulatory T cells interact with skin cells using a hormone as a messenger to generate new hair follicles and hair growth — a surprising function for the T cells.

“For the longest time, regulatory T cells have been studied for how they decrease excessive immune reactions in autoimmune diseases,” said study co-author Ye Zheng, an associate professor in Salk’s NOMIS Center for Immunobiology and Microbial Pathogenesis. “Now we’ve identified the upstream hormonal signal and downstream growth factor that actually promote hair growth and regeneration completely separate from suppressing immune response.”

“In acute cases of alopecia, immune cells attack the skin tissue, causing hair loss,” Zheng said. “The usual remedy is to use glucocorticoids [cholesterol-derived steroid hormones produced by the adrenal gland and other tissues] to inhibit the immune reaction in the skin so they don’t keep attacking the hair follicles.”

The study indicated that regulatory T cells and glucocorticoid hormones are not just immunosuppressants but also have a regenerative function.

“Applying glucocorticoids has the double benefit of triggering the regulatory T cells in the skin to produce [the protein] TGF-beta3, stimulating the activation of the hair follicle stem cells,” Zheng said.

The scientists didn’t begin by studying hair loss. They were interested in researching the roles of regulatory T cells and glucocorticoid hormones in autoimmune diseases. They first investigated how those immune components functioned in multiple sclerosis, Crohn’s disease and asthma.

They found that glucocorticoids and regulatory T cells did not function together to play a significant role in any of those conditions. So they thought they’d have more luck looking at environments in which regulatory T cells expressed particularly high levels of glucocorticoid receptors (which respond to glucocorticoid hormones), such as in skin tissue. The scientists induced hair loss in normal mice and in mice lacking glucocorticoid receptors in their regulatory T cells.

“After two weeks, we saw a noticeable difference between the mice — the normal mice grew back their hair, but the mice without glucocorticoid receptors barely could,” said study co-author Zhi Liu, a postdoctoral fellow in the Zheng lab. “It was very striking, and it showed us the right direction for moving forward.”

The findings suggested that some sort of communication must be occurring between regulatory T cells and hair follicle stem cells to allow for hair regeneration.

Using a variety of techniques for monitoring multicellular communication, the scientists then investigated how the regulatory T cells and glucocorticoid receptors behaved in skin tissue samples. They found that glucocorticoids instruct the regulatory T cells to activate hair follicle stem cells, which leads to hair growth.

This crosstalk between the T cells and stem cells depends on a mechanism in which glucocorticoid receptors induce production of TGF-beta3, all within the regulatory T cells. TGF-beta3 then activates the hair follicle stem cells to differentiate into new hair follicles, promoting hair growth. Additional analysis confirmed that this pathway was completely independent of regulatory T cells’ ability to maintain immune balance.

However, regulatory T cells don’t normally produce TGF-beta3, as they did here. When the scientists scanned databases, they found that this phenomenon occurs in injured muscle and heart tissue, similar to how hair removal simulated a skin tissue injury in this study.

Next, the scientists will look at other injury models and isolate regulatory T cells from injured tissues to monitor increased levels of TGF-beta3 and other growth factors. ◆