A surprising link between the immune system and hair growth

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Summary: Regulatory T cells interact with skin cells using glucocorticoid hormones to generate new hair follicles and promote hair growth. The findings could have positive implications for the development of new therapies to treat alopecia and other hair loss disorders.

Source: Salk Institute

Salk scientists 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 Natural 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 a very long time, regulatory T cells have been studied to find out how they decrease immune overreactions in autoimmune diseases,” says corresponding author Ye Zheng, associate professor at the NOMIS Center for Immunobiology and Microbial Pathogenesis of Salt.

“Now we have identified the upstream hormone signal and the downstream growth factor that actually promote hair growth and regeneration completely separate from suppressing the immune response.”

Scientists didn’t start by studying hair loss. They wanted to study the roles of regulatory T cells and glucocorticoid hormones in autoimmune diseases. (Glucocorticoid hormones are cholesterol-derived steroid hormones produced by the adrenal gland and other tissues.) They first studied how these immune components function in multiple sclerosis, Crohn’s disease and asthma.

They found that glucocorticoids and regulatory T cells did not work together to play a significant role in any of these conditions. Thus, they thought they would have better luck looking at environments where regulatory T cells expressed particularly high levels of glucocorticoid receptors (which respond to glucocorticoid hormones), such as in skin tissue.

Scientists induced hair loss in normal mice and mice lacking glucocorticoid receptors in their regulatory T cells.

“After two weeks, we saw a noticeable difference between the mice – the normal mice grew their hair back, but the mice without glucocorticoid receptors barely could,” says first author Zhi Liu, a postdoctoral fellow in Zheng’s lab.

“It was very striking and showed us the right direction to go forward.”

The findings suggest that some sort of communication must occur between regulatory T cells and hair follicle stem cells to enable hair regeneration.

Using various techniques for monitoring multicellular communication, the scientists then studied the behavior of regulatory T cells and glucocorticoid receptors in skin tissue samples.

They found that glucocorticoids instruct regulatory T cells to activate hair follicle stem cells, which leads to hair growth. This crosstalk between T cells and stem cells depends on a mechanism by which glucocorticoid receptors induce the production of the protein TGF-beta3, all within regulatory T cells.

It shows a man without hair
The findings suggest that some sort of communication must occur between regulatory T cells and hair follicle stem cells to enable hair regeneration. Image is in public domain

TGF-beta3 then activates hair follicle stem cells to differentiate into new hair follicles, promoting hair growth. Further analysis confirmed that this pathway was completely independent of the ability of regulatory T cells to maintain immune balance.

However, regulatory T cells do not normally produce TGF-beta3, as they did here. When the scientists scanned the databases, they found that this phenomenon occurred in injured muscle and heart tissue, similar to how hair removal simulated skin tissue injury in this study.

“In acute cases of alopecia, the immune cells attack the skin tissue, causing hair loss. The usual remedy is to use glucocorticoids to suppress the skin’s immune reaction, so that they don’t continue to attack the hair. hair follicles,” says Zheng. “The application of 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 immunosuppressants but also have a regenerative function. Next, scientists will examine other injury models and isolate regulatory T cells from injured tissue to monitor increased levels of TGF-beta3 and other growth factors.

Funding: This work was supported by a NOMIS grant and the NOMIS Foundation, the National Institute of Health (NCI CCSG P30-014195, NIA P01-454 AG073084, NIA-NMG RF1-AG064049, NIA P30-AG068635, R01-AI107027, R01- AI1511123, R21-AI154919 and S10-OD023689), the Leona M. and Harry B. Helmsley Charitable Trust, the Crohn’s and Colitis Foundation, the National Cancer Institute and Salk’s Cancer Center Core Facilities (P30-CA014195).

See also

It shows a pregnant woman

Other authors included Xianting Hu, Yuqiong Liang, Jingting Yu and Maxim N. Shokhirev from Salk and Huabin Li from Fudan University in Shanghai.

About this immune system and hair growth research news

Author: Press office
Source: Salk Institute
Contact: Press Office – Salk Institute
Image: Image is in public domain

Original research: Access closed.
“Glucocorticoid signaling and regulatory T cells collaborate to maintain the hair follicle stem cell niche” by Ye Zheng et al. Natural immunology


Summary

Glucocorticoid signaling and regulatory T cells collaborate to maintain the hair follicle stem cell niche

Maintenance of tissue homeostasis depends on communication between stem cells and supporting cells in the same niche. Regulatory T cells (Tregister cells) appear as an essential part of the stem cell niche to support their differentiation.

How Tregister the dynamic signals cells detect in this microenvironment and communicate with stem cells are mostly unknown. In the present study, using hair follicles (HF) to study Tregister cell-stem cell crosstalk, we show an unrecognized function of the steroid hormone glucocorticoid in the instruction of resident T of the skinregister to facilitate HF stem cell (HFSC) activation and HF regeneration.

Ablation of the glucocorticoid receptor (GR) in Tregister blocks hair regeneration without affecting immune homeostasis. Mechanically, GR and Foxp3 cooperate at Tregister cells to induce transforming growth factor β3 (TGF-β3), which activates Smad2/3 in HFSCs and facilitates HFSC proliferation.

The present study identifies the crosstalk between Tregister cells and HFSCs mediated by the GR–TGF-β3 axis, highlighting a possible way to manipulate Tregister cells to support tissue regeneration.

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