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Scientists at the Salk Institute (USA) have discovered an unexpected molecular target of a common treatment for alopecia, a condition in which a person’s immune system attacks their own hair follicles, causing hair loss. The findings, published in Nature Immunology, describe how immune cells called regulatory T cells interact with the skin cells using a hormone as a messenger to generate new hair follicles and hair growth.
“Regulatory T cells have long been studied for how they decrease excessive immune reactions in autoimmune diseases,” says the corresponding author. Ye Zheng.
“We have now identified the upstream hormonal signal and the downstream growth factor that actually promote hair growth and regrowth completely independent of suppression of the immune response.”
Scientists did not start by studying hair loss. They were interested in investigating the role of regulatory T cells and glucocorticoid hormones in autoimmune diseases. (Glucocorticoid hormones are steroid hormones derived from cholesterol and produced by the adrenal gland and other tissues.) They first investigated the functioning of these immune components in the multiple sclerosis, Crohn’s disease and asthma.
They found that glucocorticoids and regulatory T cells did not work together to play a major role in any of these diseases. So they thought they would have better luck looking for environments in which regulatory T cells express especially high levels of glucocorticoid receptors (which respond to glucocorticoid hormones), such as in skin tissue. The scientists induced hair loss in normal mice and mice who lacked glucocorticoid receptors on their regulatory T cells.
“After two weeks, we saw a noticeable difference between the mice: the normal mice grew hair back, but the mice lacking glucocorticoid receptors hardly grew any,” explains first author Zhi Liu, a postdoctoral fellow at the Zheng’s lab. “It was very eye-catching and showed us the right direction to move forward.”
The findings suggest thate there must be some kind of communication between regulatory T cells and stem cells from the hair follicle to allow hair regrowth.
Using various techniques to control multicellular communication, the scientists investigated how regulatory T cells and glucocorticoid receptors behave in skin tissue samples.
They found that glucocorticoids instruct regulatory T cells to activate hair follicle stem cells, leading to hair growth. This interrelationship between T cells and stem cells depends on a mechanism by which glucocorticoid receptors induce the production of the TGF-beta3 protein, all within regulatory T cells.
TGF-beta3 then activates the hair follicle stem cells to differentiate into new hair follicles, promoting hair growth. Further analyzes confirmed that this pathway was completely independent of the ability of regulatory T cells to maintain immune balance.
However, regulatory T cells do not usually produce TGF-beta3, as was the case in this case. When the scientists scrutinized the databases, they found that this phenomenon occurs in injured heart and muscle tissue, similar to how hair removal simulated injury to skin tissue in this study.
“In acute cases of alopecia, immune cells attack skin tissue, causing hair loss. The usual remedy is to use glucocorticoids to suppress the immune reaction in the skin, so they don’t continue to attack the hair follicles,” says Zheng. “Applying glucocorticoids has the dual benefit of triggering regulatory T cells in the skin to produce TGF-beta3, stimulating the activation of hair follicle stem cells.”
This study revealed that regulatory T cells and glucocorticoid hormones are not only immunosuppressive, but also have a regenerative function. Next, scientists will study other injury models and isolate regulatory T cells from injured tissues to monitor increased levels of TGF-beta3 and other growth factors.
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