inflammation & autoimmunity

joint & tendon health

TYK2

Adjusting Inflammatory Cytokines in Rheumatoid Arthritis (TYK2)

Written by Jasmine Foster, BSc, BEd on November 24th, 2020

The TYK2 gene encodes tyrosine kinase 2, which regulates interferons and cytokines. What is its role in rheumatoid arthritis? Find out here.

Summary

TYK2 encodes tyrosine kinase 2. Variants of TYK2 may play a role in rheumatoid arthritis by altering the production of inflammatory cytokines. Lifestyle, diet, and supplement modifications may counteract the effects of these variants by decreasing IL-12 and IL-23.

TYK2 and Rheumatoid Arthritis

The TYK2 gene encodes tyrosine kinase 2, a member of the JAK protein family. Members of the JAK family activate STAT (‘Signal transducer and activator of transcription’) proteins in response to cytokines [R, R].

TYK2 is believed to play a role in the antiviral immune response through the interferon pathways. Mutations that interfere with the function of TYK2 have been associated with immune deficiency [R].

Other variants, however, may be protective against autoimmune diseases like rheumatoid arthritis. Multiple studies across different countries and ethnicities have found that the rare protective allele of one variant was significantly less common in rheumatoid arthritis patients than in the general population. [R, R, R, R].

The TYK2 enzyme regulates multiple cytokine signals, significantly altering the expression of IL-6, IL-10, IL-12, and IL-23, among others. Mice without functional TYK2 have compromised IFN-α, IL-12, and IL-23 pathways, but intact IL-6 and IL-10 pathways [R].

The TYK2 gene encodes a JAK protein that regulates the expression of inflammatory cytokines and interferons. It plays a role in antiviral immunity and may promote autoimmune inflammation.

A Secondary Association: ICAM3

The major TYK2 variant that appears to protect against rheumatoid arthritis, rs34536443, is physically close to another gene, ICAM3, and may affect its expression as well [R].

The ICAM3 gene encodes an intercellular adhesion molecule (ICAM) that helps white blood cells stick to other tissues and move around the body. Researchers believe that, in addition to helping white blood cells move, ICAM3 sends important signals during an inflammatory immune response. It has also been implicated in inflammatory signalling in cancer, and it helps clear dead white blood cells from the body [R, R, R].

The role of ICAM3 in rheumatoid arthritis is not well-studied, but it certainly contributes to inflammation and white blood cell activity.

The TYK2 variant rs34536443 also affects ICAM3, a cell adhesion protein that helps white blood cells move around the body.

Your TYK2 Results for Rheumatoid Arthritis

SNP Table

variant	genotype	frequency	risk allele
rs34536443

TYK2 rs34536443

‘G’ = Associated with average rates of rheumatoid arthritis
‘C’ = Possibly protective against rheumatoid arthritis
The ‘C’ allele may reduce the activity of TYK2 and ICAM3 and suppress the production of inflammatory cytokines [R, R].

Recommendations

Sunlight & Vitamin D

Moderate sun exposure is the best way to get natural UV light and vitamin D, which both help suppress inflammation. Vitamin D supplementation lowered IL-12 levels in some human studies but not in others. In a study on 57 people with lupus, vitamin D deficiency was associated with increased IL-23 levels. Both IL-12 and IL-23 signals rely on TYK2 [R, R, R, R, R].

Vitamin D deficiency is more common in patients with rheumatoid arthritis than in the general population [R].

A study of nurses found that those with greater exposure to UVB rays from the sun had the lowest rates of rheumatoid arthritis. Another study found that people who live further from the equator (who are likely to be exposed to less sunlight on average) are more likely to develop rheumatoid arthritis [R, R].

According to multiple studies, people with a higher intake of vitamin D appear less likely to develop rheumatoid arthritis. However, there are conflicting reports on whether supplementing with vitamin D can improve pain in existing rheumatoid arthritis cases [R, R, R].

Vitamin D supplementation decreases IL-12 and IL-23 and may improve the symptoms of rheumatoid arthritis.

Omega-3 Fatty Acids

Omega-3 fatty acids found in fatty fish, EPA and DHA, may inhibit Th17 cells and lower the levels of IL-17 and IL-23. IL-23 signalling, in turn, relies on TYK2 [R, R, R].

Omega-3 fats can also inhibit STAT3, a downstream target of the JAK enzymes [R].

Studies suggest that increased dietary intake of omega-3 fatty acids may protect against rheumatoid arthritis. In a meta-analysis of 20 clinical trials, higher omega-3 consumption improved rheumatoid arthritis symptoms and lab markers [R, R].

Good dietary omega-3 sources include [R]:

Fish and seafood
Flaxseed
Chia seeds
Walnuts
Hemp seeds

Fish oil is also a good supplementary source of DHA and EPA.

Omega-3 fatty acids decrease IL-23 and may protect against rheumatoid arthritis.

Thunder God Vine

Celastrol, an active compound of thunder god vine (Tripterygium wilfordii), may reduce the production of inflammatory cytokines including IL-12 and IL-23 [R, R].

In 2 clinical trials, thunder god vine extract (60-360 mg/day) improved joint inflammation and pain from rheumatoid arthritis. It was more effective than the anti-rheumatic drug sulfasalazine in another trial on 62 people [R, R, R].

Similarly, its tincture applied on the skin improved rheumatoid arthritis in a trial on 61 people [R].

Thunder god vine and its active components also improved arthritis in multiple animal studies [R, R, R, R, R, R, R, R, R, R, R, R].

Celastrol, an active compound of thunder god vine, may decrease IL-12 and IL-23 and improve rheumatoid arthritis symptoms.

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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