A surprising link between the immune system and hair growth

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 for the treatment of 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 to fall.

The results, published in Immunology of nature 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 long time, regulatory T cells have been studied for how they reduce excessive immune reactions in autoimmune diseases,” says corresponding author Ye Zheng, an associate professor at Salk’s NOMIS Center for Immunobiology and Microbial Pathogenesis.

“We have now identified the upstream hormone signal and downstream growth factor that actually promote hair growth and regeneration completely separated by suppression of the immune response.”

Scientists didn’t start by studying hair loss. They were interested in researching the roles of regulatory T lymphocytes 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 work 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. Hence, 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: normal mice regrown their hair, but mice without glucocorticoid receptors could barely do it,” says first author Zhi Liu, a postdoctoral fellow in the lab. Zheng.

“It was very surprising and showed us the right direction to move forward.”

The results suggested that some sort of communication must occur between regulatory T cells and hair follicle stem cells to allow for hair regeneration.

Using a variety of techniques to monitor multicellular communication, the scientists then studied the behavior of regulatory T lymphocytes and glucocorticoid receptors in skin tissue samples.

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

The results suggested that some sort of communication must occur between regulatory T cells and hair follicle stem cells to allow for hair regeneration. The image is in the public domain

TGF-beta3 then activates 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 normally produce TGF-beta3, as they have done here. When the scientists scanned the databases, they found that this phenomenon occurs in injured muscles and heart tissue, similar to how hair removal simulated skin tissue injury in this study.

“In acute cases of alopecia, immune cells attack the skin tissue, causing hair loss. The usual remedy is to use glucocorticoids to inhibit the immune reaction in the skin, so they don’t keep attacking the hair follicles, “says Zheng.” The application of glucocorticoids has the double benefit of activating regulatory T cells in the skin to produce TGF-beta3, stimulating the activation of hair follicle stem cells “.

This study revealed that regulatory T lymphocytes and glucocorticoid hormones are not only immunosuppressive but also have a regenerative function. Next, the scientists will look at other injury patterns and isolate regulatory T cells from damaged tissues to monitor for increased levels of TGF-beta3 and other growth factors.

Financing: This work was supported by a NOMIS fellowship 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), Leona M. and Harry B. Helmsley Charitable Trust, Crohn’s and Colitis Foundation, National Cancer Institute and Salk’s Cancer Center Core Facilities (P30-CA014195).

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Other authors included Xianting Hu, Yuqiong Liang, Jingting Yu, and Maxim N. Shokhirev of Salk; and Huabin Li of 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: The image is in the public domain

Original research: Closed access.
“Glucocorticoid signaling and regulatory T cells work together to maintain the hair follicle stem cell niche” by Ye Zheng et al. Immunology of nature


Abstract

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

The maintenance of tissue homeostasis depends on the communication between the stem cells and the supporting cells in the same niche. Regulatory T lymphocytes (T.reg cells) are emerging as a critical component of the stem cell niche to support their differentiation.

Like treg cells perceive dynamic signals in this microenvironment and communicate with stem cells is mostly unknown. In the present study, using hair follicles (HF) to study T.reg stem-cell crosstalk, we show an unrecognized function of the glucocorticoid steroid hormone in instructing skin-resident Treg cells to facilitate HF stem cell (HFSC) activation and HF regeneration.

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

The present study identifies crosstalk between T.reg cells and HFSC mediated by the GR – TGF-β3 axis, highlighting a possible means to manipulate Treg cells to support tissue regeneration.

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