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IKZF4

Are Regulatory T Cells Essential for Preventing Hair Loss? (IKZF4)

Written by Jasmine Foster, BSc, BEd on December 30th, 2020

The IKZF4 gene encodes a protein that is essential for the production of Tregs. What is its connection to alopecia areata? Read on to find out.

Summary

IKZF4 encodes IKAROS family zinc finger 4, also known as Eos. Variants of IKZF4 may play a role in alopecia areata by interfering with the production or activity of Tregs. Lifestyle, diet, and supplement modifications may counteract the effects of these variants by directly supporting Eos or increasing Treg numbers and activity.

IKZF4 and Alopecia Areata

The IKZF4 gene encodes a protein called IKAROS family zinc finger 4 or “Eos,” which is involved in the development of white blood cells (T cells, B cells, and natural killer cells) [R].

Eos is essential for the correct development of regulatory T cells (Tregs), anti-inflammatory immune cells that prevent an immune response to normal, non-threatening cells and proteins. In mice lacking the Eos protein, Tregs failed to send tolerance signals to the immune system, and the animals developed systemic autoimmune disease [R, R].

Unsurprisingly, variants in the IKZF4 gene that lead to defects in Eos have been associated with various autoimmune conditions, including type 1 diabetes and alopecia areata. In type 1 diabetes, reduced Eos and impaired Tregs may lead to the production of autoantibodies against insulin and certain cell types in the pancreas [R].

In alopecia areata, reduced Eos and impaired Tregs may lead to the production of autoantibodies against a wide variety of tissue types [R].

The IKZF4 gene encodes a protein called Eos which is essential for the production of anti-inflammatory Tregs and the suppression of autoimmune inflammation. Variants that reduce Eos are associated with alopecia areata.

Your IKZF4 Results for Alopecia Areata

SNP Table

variant	genotype	frequency	risk allele
rs1701704

IKZF4 rs1701704 [R]

‘T’ = Not associated with alopecia areata
‘G’ = Associated with relatively higher rates of alopecia areata
The ‘G’ allele may reduce Eos protein activity, leading to lower Treg levels and increased autoimmune inflammation [R, R].

Recommendations

Zinc

Eos (IKZF4) is a zinc-finger protein, meaning that it contains a structure called a zinc finger that requires zinc to function correctly [R].

People with alopecia areata are more likely to be deficient in zinc than the general population. Furthermore, in a small study, the majority of alopecia areata patients showed some improvement of symptoms after twelve weeks of taking oral zinc supplements [R].

A study of 342 people associated patchy (alopecia areata) and diffuse (telogen effluvium) hair loss with low blood zinc levels. The authors suggested that disturbed zinc metabolism plays a key role in these conditions [R].

In line with this, zinc supplementation improved both conditions in 2 small uncontrolled trials of 20 people who also had zinc deficiency. In a non-placebo-controlled trial of 73 women complaining of hair loss, zinc was especially effective when combined with calcium pantothenate [R, R, R].

Good dietary sources of zinc include red meat, seafood, dairy products, nuts, legumes, and whole grains [R].

The daily recommended intake of zinc is 11 mg per day for men and 8 mg for women. However, benefits for alopecia areata patients have only been demonstrated at daily doses of 50 mg per day [R, R, R].

Eos requires zinc in order to function correctly, and supplemental zinc has been found to improve alopecia areata in some patients.

Avoid Cigarettes

Cigarette smoke exposure may increase inflammation by dysregulating Tregs. People with reduced Eos activity because of IKZF4 variants may be at greater risk of inflammation from cigarette smoke [R, R].

In a study of over 60,000 people, of whom 154 developed patchy hair loss (alopecia areata), smoking was associated with an approximately 2-fold incidence of this condition. Cigarette smoke may cause oxidative and inflammatory damage in the hair follicles, and impair hair growth [R, R].

Cigarette smoke exposure may dysregulate Tregs and increase the risk of hair loss.

Vitamin D

Vitamin D is believed to increase the numbers and activity of circulating Treg cells in people with inflammatory diseases. This effect may make it especially important for people with detrimental IKZF4 variants to avoid vitamin D deficiency [R].

Low blood vitamin D levels have been associated with increased incidence, severity, and duration of patchy hair loss (alopecia areata) in multiple studies [R, R, R, R, R].

In an uncontrolled trial of 48 people with this condition, a synthetic derivative of vitamin D (calcipotriol) applied to the scalp for 12 weeks caused hair regrowth of at least 50% in 75% of the patients and full regrowth in 27%. Both this chemical and UV-B radiation (which stimulates vitamin D production) were similarly effective in a placebo-controlled trial of 60 people [R, R].

To avoid vitamin D deficiency, the National Institutes of Health recommends 20 mcg of vitamin D per day. If you are using a topical cream, be sure to follow the instructions on the label or consult with your doctor about appropriate use [R].

Vitamin D may increase circulating Tregs and suppress autoimmune inflammation, which may make it beneficial for both preventing and improving alopecia areata.

Jasmine Foster

BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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Are Regulatory T Cells Essential for Preventing Hair Loss? (IKZF4)

Summary

IKZF4 and Alopecia Areata

Your IKZF4 Results for Alopecia Areata

SNP Table

Recommendations

Zinc

Avoid Cigarettes

Vitamin D

Disclaimer

More skin & beauty blogs

Content

Unlock Personalized Results And So Much More!

Essential Bundle

Essential

Bundle

Limited time offer 25% off

Ultimate Bundle

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About

Navigation

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