Discover the relationship between the immune system and hair growth

Alopecia is usually treated with glucocorticoids, which are steroid hormones capable of suppressing the immune reaction in the skin. A team from the Salk Institute discovered that these hormones not only act as immunosuppressants, but also have regenerative activity involving specific immune cells.

Alopecia: When the immune system goes off track

Alopecia is an autoimmune disease characterized by accelerated hair loss. In the case of alopecia ariata (also called alopecia areata), the immune system mistakenly attacks the hair follicle – causing more or less hair to fall out. Ye Zheng, associate professor at the NOMIS Center for Immunobiology and Microbial Diseases, and his collaborators were interested in the role of regulatory T cells (Treg) and glucocorticoid hormones in autoimmune diseases. In particular, they looked closely at the action of these immune components in multiple sclerosis, Crohn’s disease, and asthma.

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Treg cells are very important for maintaining homeostasis. Its role is to inhibit the activity of autologous lymphocytes, which attack healthy cells in the body. Therefore they are essential for maintaining immune tolerance. ” For a long time, regulatory T cells have been studied to see how they reduce excessive immune responses in autoimmune diseases Cheng says.

Although both Treg cells and glucocorticoids have an immunosuppressive effect, the researchers found that they did not play a significant role in any of the autoimmune diseases considered. They then set out to examine environments in which Treg cells express particularly high levels of glucocorticoid receptors, such as in skin tissue.

Communication between Treg cells and stem cells

The researchers note that maintaining tissue homeostasis depends on communication between stem cells and support cells of the same niche nature’s immunity. Treg cells emerge as an essential component of the stem cell niche to support their differentiation. However, it has not been clear how Treg cells sense dynamic signals in the tissue microenvironment and communicate with stem cells.

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To better understand this method of communication, the researchers used mouse hair follicles for the first time. They shaved the backs of normal mice and other mice lacking Treg cells for glucocorticoid receptors. After two weeks, the latter showed almost no signs of regrowth, while the hair of the normal mice grew completely.

Left: After hair loss, normal mouse skin cells (blue) activate hair follicle stem cells (purple). Right: cells of mice lacking the glucocorticoid receptor in their Treg cells cannot activate hair follicle stem cells. Conclusion: These receptors are essential in the treatment of baldness.

These results confirm that some kind of communication must occur between Treg cells and hair follicle stem cells to enable hair regeneration. After this experiment in mice, the researchers studied the behavior of Treg cells and glucocorticoid receptors in skin tissue samples. They found that glucocorticoids “directed” Treg cells to activate hair follicle stem cells, which leads to hair growth.

A messenger that stimulates the formation of new hair follicles

Further analyzes confirmed that this pathway was completely independent of the ability of Treg cells to maintain immune homeostasis: ablation of glucocorticoid receptors in Treg cells prevents hair regeneration without affecting immune homeostasis.

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This communication between Treg cells and stem cells is based on a mechanism by which glucocorticoid receptors stimulate production of the TGF-β3 protein (a transforming growth factor, involved in cell differentiation) within Treg cells. This protein then activates hair follicle stem cells to transform into new hair follicles.

We have now identified an upstream hormone and downstream growth factor signaling that actually promote hair growth and regeneration, independent of immune response suppression. Cheng says. In other words, researchers have discovered a potential way to manipulate Treg cells to support tissue regeneration.

Normally, Treg cells do not produce TGF beta 3. And when the scientists looked into this, they found that the phenomenon also occurs in injured muscle and heart tissue—just as hair removal simulated the injury to skin tissue in this study. The team now plans to examine other infection models and isolate Treg cells from injured tissues to monitor levels of TGF-beta 3 and other growth factors.

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