In experiments in mice, UC San Francisco researchers have found that regulatory T cells (Tregs; pronounced “tee-regs”), a kind of immune cell generally associated with controlling inflammation, directly result in stem cells in the skin to promote healthy hair growth. Those immune cells as partners, the researchers found, the particular stem cells cannot regenerate hair follicles, leading to baldness.
“Our hair follicles are constantly recycling where possible: when a hair falls out, the whole hair follicle needs to grow back, ” said Michael Rosenblum, MD, PhD, an assistant professor of dermatology at UCSF plus senior author on the new paper. “This has been considered to be an entirely stem cell-dependent process, but it turns out Tregs are crucial. If you knock out this one immune cell type, curly hair just doesn’t grow. ”
The new research — published online May 26 in Cell — suggests that defects in Tregs could be responsible for alopecia areata, a common autoimmune disorder that triggers hair loss, and could potentially play a role in other forms of baldness, which includes male pattern baldness, Rosenblum said. Since the same stem tissue are responsible for helping heal the skin after injury, the study increases the possibility that Tregs may play a key role in injury repair as well.
Anti-inflammatory immune tissue directly activate skin stem cells
Normally Tregs act as peacekeepers and diplomats, informing all of those other immune system of the difference between friend and foe. Whenever Tregs don’t function properly, we may develop allergies in order to harmless substances like peanut protein or cat dander, or suffer from autoimmune disorders in which the immune system turns on the human body’s own tissues.
Like other immune tissue, most Tregs reside in the body’s lymph nodes, but some reside permanently in other tissues, where they seem to have progressed to assist with local metabolic functions as well as playing their particular normal anti-inflammatory role. In the skin, for example , Rosenblum plus colleagues have previously shown that Tregs help set up immune tolerance to healthy skin microbes in newborn baby mice, and these cells also secrete molecules that assist with wound healing into adulthood.
Rosenblum, who is each an immunologist and a dermatologist, wanted to better understand the function of these resident immune cells in skin health. To get this done, he and his team developed a technique for temporarily eliminating Tregs from the skin. But when they shaved patches associated with hair from these mice to make observations of the affected epidermis, they made a surprising discovery. “We quickly noticed that the particular shaved patches of hair never grew back, and thought, ‘Hmm, now that’s interesting, ‘” Rosenblum stated. “We realized we had to delve into this further. ”
In the new research, led by UCSF postdoctoral fellow and first author Niwa Ali, PhD, various lines of evidence suggested that Tregs play a role within triggering hair follicle regeneration.
First, image resolution experiments revealed that Tregs have a close relationship with all the stem cells that reside within hair follicles and allow these to regenerate: the number of active Tregs clustering around follicle originate cells typically swells by three-fold as follicles your growth phase of their regular cycle of rest and reconstruction. Also, removing Tregs from the skin blocked hair growth only if this was done within the first three days right after shaving a patch of skin, when follicle revitalization would normally be activated. Getting rid of Tregs later on, after the regeneration had already begun, had no effect on tresses regrowth.
Tregs’ role in triggering hair regrowth did not appear related to their normal ability to tamp lower tissue inflammation, the researchers found. Instead, they learned that Tregs trigger stem cell activation directly through a typical cell-cell communication system known as the Notch pathway. First, the particular team demonstrated that Tregs in the skin express abnormally high levels of a Notch signaling protein called Spectacular 1 (Jag1), compared to Tregs elsewhere in the body. They then demonstrated that removing Tregs from the skin significantly reduced Level signaling in follicle stem cells, and that replacing Tregs with microscopic beads covered in Jag1 protein refurbished Notch signaling in the stem cells and successfully triggered follicle regeneration.
“It’s as if the skin come cells and Tregs have co-evolved, so that the Tregs not just guard the stem cells against inflammation but also be a part of their regenerative work, ” Rosenblum said. “Now the particular stem cells rely on the Tregs completely to know if it’s time to start regenerating. ”
Research could lead to new treatments for autoimmune hair loss
Rosenblum said the findings may have implications pertaining to alopecia areata, an autoimmune disease that interferes with hair follicle regeneration and causes patients to lose hair in spots from their scalp, eyebrows, and faces. Alopecia is among the most typical human autoimmune diseases — it’s as common since rheumatoid arthritis, and more common than type 1 diabetes — but scientists have little idea what causes it.
After his team first observed hair loss in Treg-deficient mice, Rosenblum learned that the genes associated with alopecia within previous studies are almost all related to Tregs, and remedies that boost Treg function have been shown to be an effective therapy for the disease. Rosenblum speculates that better understanding Tregs’ critical role in hair growth could lead to improved treatments regarding hair loss more generally.
The study also contributes to a growing sense that immune cells play much wider roles in tissue biology than had previously already been appreciated, said Rosenblum, who plans to explore whether Tregs in the skin also play a role in wound healing, because the same follicle stem cells are involved in regenerating skin subsequent injury.
“We think of immune cells because coming into a tissue to fight infection, while come cells are there to regenerate the tissue after it can damaged, ” he said. “But what we found the following is that stem cells and immune cells have to come together to make regeneration possible. ”