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Tregs: Hair Loss Linked to Faulty Immune Cells

tregs hair loss

It seems like every week there’s a new ‘breakthrough’ baldness cure. And while the reality often seems to fall short of the headlines, each discovery takes us a step closer to beating baldness. The most recent such discovery is the role of tregs in hair loss. Without these anti-inflammatory immune cells, new hair cannot be formed. This has led scientists to speculate that defective tregs may be the cause of alopecia areata, and raises the possibility of new treatments for other forms of hair loss too.

What are tregs?

Tregs, or t-regs, are a type of immune cell that help the immune system decide what – and what not – to attack.

The immune system removes harmful foreign agents, such as viruses, from the body. Tregs are what help the immune system distinguish friend from foe. They also help control inflammation.

But if tregs aren’t functioning correctly, the immune system may misidentify and destroy its own cells, mistaking them for foreign invaders. This is what happens in the case of alopecia areata, an autoimmune hair loss disorder.

Tregs and alopecia areata

Alopecia areata is typically characterised by circular patches of hair loss on the scalp. More severe forms, alopecia totalis and alopecia universalis, cause hair to be lost from the entire scalp and the entire body respectively.

It is well understood that these forms of hair loss occur when the immune system attacks hair follicles. However, it has largely remained a mystery as to why this happens. A new study, published this month in the medical journal Cell, suggests that tregs may provide the answer.

Studying the effects of tregs on overall skin health in mice, researchers made an unexpected discovery: removing tregs prevented hair from growing back.

Defects in tregs prevent the immune system from recognising the body’s own hair cells. If this is what causes alopecia areata, then restoring normal treg function may lead to a cure for this rare autoimmune disorder.

These findings back up research reported in this genome-wide association study from 2010. The study looked at the genes of over a thousand subjects with alopecia areata and found mutations on genes involved with treg function.

tregs hair loss genetic study (alopecia areata)

This more recent study has implications beyond alopecia areata, though. The study on mice also found a link between tregs and stem cells, which may lead to new treatments for more common forms of hair loss as well.

Stem cells

Hair follicles go through various cycles of growth and rest. When a hair falls out, the follicle has to grow back. But without stem cells, this doesn’t happen.

And what the research on mice demonstrated was that without tregs, stem cells were not activated. It seems that tregs are important for more than just immune response regulation.

Researchers further revealed that this stem cell activation occurs via the Notch signalling pathway and a protein known as Jag1. Artificially increasing Jag1 stimulated new hair growth in the mice, just as tregs normally would.

Prof. Michael Rosenblum, co-author of the study, said:

“Our hair follicles are constantly recycling. When a hair falls out, the whole hair follicle has to grow back. This has been thought to be an entirely stem cell-dependent process, but it turns out tregs are essential […] It’s as if the skin stem cells and tregs have co-evolved. […] The stem cells rely on the tregs completely to know when it’s time to start regenerating.”

So, no tregs = no stem cells. And without stem cells, hair is not regenerated after a hair cycle.

Perhaps related: studies have shown that there are significant differences in stem cell activity between bald and non-bald scalps. Might this be a consequence of defective tregs?

Either way, stem cells are what kick-start the hair regeneration process during healthy hair cycling. And if tregs increase these stem cells, this may lead to new hair loss treatments – or even a cure.

Tregs and pattern hair loss?

Pattern hair loss, or androgenetic alopecia, is by far the most common form of hair loss worldwide. It’s estimated that it affects as many as 70% of men and 40% of women at some stage in their lives.

Androgenetic alopecia has long been thought to be caused by hormones – specifically dihydrotestosterone (DHT).

Hair loss treatments that reduce DHT are effective at preventing further hair loss but are less effective at actually regrowing lost hair. However, more recent hair loss treatments/discoveries – derma rolling, platelet-rich plasma (PRP), and hair plucking (quorum sensing), for example – appear to work by increasing stem cells in bald areas. While these treatments have not been studied as thoroughly, they appear to be far more effective for regrowth.

So, if tregs increase stem cells, could they regrow lost hair and cure baldness?

This remains to be seen. For one, it’s unclear whether men and women with androgenetic alopecia have defective tregs in the first place. The association between tregs and alopecia areata is pretty well established, but it is unclear whether this holds for more common forms of hair loss.

Interestingly, though, tregs are known to guard against inflammation. And since inflammation almost always accompanies pattern hair loss, it increases the likelihood that defective tregs may play a role in this hair loss condition as well.

In summary

  • Tregs tell the immune system what to attack or not attack. This may be useful for treating alopecia areata and other autoimmune diseases.
  • A new study suggests tregs are also necessary for stem cell activation in hair follicles.
  • Without stem cells, hair follicles do not regenerate after a hair cycle.
  • This could lead to new treatments for hair regrowth – but only if hair loss is caused by treg defects in the first place.

Regardless of whether defective tregs play a role in androgenetic alopecia, it is clear these immune cells play a crucial role in alopecia areata and other autoimmune disorders.

And the discovery that tregs also play a key role in stem cell activation is an exciting addition to our understanding of hair loss and wound healing. However, it remains to be seen whether these findings lead to new therapies for hair loss.

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