Salk scientists have uncovered 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 on June 23, 2022, 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.
“For the longest time, regulatory T cells have been studied for how they decrease excessive immune reactions in autoimmune diseases,” says corresponding author Ye Zheng, 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.”
The scientists induced hair loss in normal mice and mice lacking glucocorticoid receptors in their regulatory T cells.
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 the stem cells depends on a mechanism whereby glucocorticoid receptors induce production of the protein 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.
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.
This study revealed that regulatory T cells and glucocorticoid hormones are not just immunosuppressants but also have a regenerative function. 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.
Liu, Z., Hu, X., Liang, Y. et al. Glucocorticoid signaling and regulatory T cells cooperate to maintain the hair-follicle stem-cell niche. Nat Immunol, 2022 DOI: 10.1038/s41590-022-01244-9
Salk Institute. (2022, June 23). Hair-raising research: Scientists find surprising link between immune system, hair growth: Study highlights how current treatments for alopecia work on a cellular level. ScienceDaily. Retrieved May 9, 2023 from www.sciencedaily.com/releases/2022/06/220623110948.htm
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