SAN FRANCISCO — Researchers have discovered that regulatory T cells, or Tregs, a type of immune cell generally associated with controlling inflammation, directly trigger stem cells in the skin to promote healthy hair growth.
The researchers at the University of California, San Francisco (UCSF), found in a mice study published online this week in Cell that without these immune cells as partners, the stem cells cannot regenerate hair follicles, leading to baldness.
“Our hair follicles are constantly recycling: when a hair falls out, the whole hair follicle has to grow back,” said Michael Rosenblum, an assistant professor of dermatology at UCSF and senior author on the study. “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.”
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, they may lead to allergies to harmless substances like peanut protein or cat dander, or to autoimmune disorders in which the immune system turns on the body’s own tissues. Like other immune cells, most Tregs reside in the body’s lymph nodes, but some live permanently in other tissues, where they seem to have evolved to assist with local metabolic functions as well as playing their normal anti-inflammatory role.
In the skin, for example, Rosenblum and his colleagues have previously shown that Tregs help establish immune tolerance to healthy skin microbes in newborn mice, and these cells also secrete molecules that help with wound healing into adulthood.
For the new study, the team developed a technique for temporarily removing Tregs from the skin. When they shaved patches of hair from these mice to make observations of the affected skin, they made a surprising discovery. “We quickly noticed that the shaved patches of hair never grew back, and we thought, ‘that’s interesting,'” Rosenblum was quoted as saying in a news release. “We realized we had to delve into this further.”
The research, led by UCSF postdoctoral fellow and first author Niwa Ali, suggested that Tregs play a role in triggering hair follicle regeneration.
First, imaging experiments revealed that 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. And, 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.
In addition, Tregs’ role in triggering hair growth did not appear related to their normal ability to tamp down tissue inflammation. Instead, the team discovered that Tregs trigger stem cell activation directly through a common cell-cell communication system known as the Notch pathway. And removing Tregs from the skin significantly reduced Notch signaling in follicle stem cells.
“It’s as if the skin stem cells and Tregs have co-evolved, so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work,” Rosenblum said. “Now the stem cells rely on the Tregs completely to know when it’s time to start regenerating.” (Xinhua)