inflammation & autoimmunity

gut health

IRF5

How Does This Gene Stimulate Th1 and Promote IBD? (IRF5)

Written by Jasmine Foster, BSc, BEd on May 18th, 2020

IRF5 stimulates the Th1 response, suppresses IL-10, and may promote the development of ulcerative colitis. Do you have this inflammatory allele? Read on to learn more.

What is IRF5?

IRF5 (interferon regulatory factor 5) regulates the expression of interferons and promotes Th1 and Th17 inflammatory responses. Macrophages, a type of white blood cell responsible for consuming invading pathogens, express a high level of IRF5; in these cells, IRF5 stimulates the release of proinflammatory interleukins and suppresses the anti-inflammatory IL-10 [R].

IRF5 has, unsurprisingly, been implicated in a variety of inflammatory diseases, including cancer, lupus erythematosus, and ulcerative colitis [R, R, R].

What is Ulcerative Colitis?

IBD is a group of autoimmune diseases characterized by inflammation and sores in the gut lining, which can result in diarrhea, abdominal pain, fatigue, fever, rectal bleeding, nutritional deficiencies, and weight loss. The definition of IBD includes both ulcerative colitis and Crohn’s disease [R].

Ulcerative colitis (UC) differs from Crohn’s disease in that it produces chronic inflammation and ulceration of the large intestine (the colon) and is also focused in the innermost lining of the colon wall, where Crohn’s can damage much broader swaths of tissue [R, R, R].

IRF5 in Inflammatory Disease

A normal inflammatory response protects your body from invading pathogens like bacteria and viruses. However, inflammation can easily get out of control and do serious damage. IRF5 may cause the worst damage by over-activating macrophages and stimulating the production of too many inflammatory cytokines [R].

People with IBD may have irregular macrophage numbers and activity. Some studies suggest that in IBD, macrophages do not differentiate correctly into non-inflammatory cells; instead, they continue to produce inflammatory cytokines well after an infection is resolved [R, R].

Inhibiting IRF5 has been proposed as a potential drug target for diseases, including IBD, in which macrophages may be responsible for excessive inflammation [R].

IRF5 increases the Th1 response, suppresses IL-10, and promotes inflammation. In ulcerative colitis, IRF5 may cause macrophages to continue producing inflammatory signals even after an infection is resolved.

IRF5 Variants & Ulcerative Colitis

At least one IRF5 variant, rs4728142, has been linked to ulcerative colitis. At this SNP, the uncommon ‘A’ allele is associated with increased inflammation and rates of disease [R].

The risk allele’s effect on gene expression has not specifically been studied in IBD, but it almost certainly increases IRF5, thereby stimulating inflammation. The same allele of the same SNP is also associated with systemic lupus erythematosus (SLE), an autoimmune inflammatory disease likewise associated with hyper-activated IRF5 [R, R].

In addition to stimulating the production of inflammatory cytokines, IRF5 suppresses the production of anti-inflammatory IL-10; this is another mechanism by which IRF5 mutations may contribute to out of control inflammation [R].

At rs4728142, the ‘A’ allele is associated with increased rates of ulcerative colitis. This variant very likely causes increased expression or activity of IRF5.

Your IRF5 Results for IBD

You may try the complementary approaches listed below if you and your doctor determine that they could be appropriate for you. Discuss the strategies listed here with your doctor. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.

SNP Table

variant	genotype	frequency	risk allele
rs4728142

SNP Summary and Table

IRF5 rs4728142

‘G’ = Not associated with ulcerative colitis
‘A’ = Associated with ulcerative colitis; likely to increase IRF5 expression and suppress IL-10
About half of all people worldwide have at least one copy of the ‘A’ allele.
The ‘A’ allele is more common in people of European (69%) and South Asian (63%) descent and much less common in people of East Asian descent (19%).

Recommendations

Lifestyle

Moderate Sun Exposure

Exposure to UVB rays has been found to inhibit the Th1 immune response, which is activated by IRF5. Moderate sun exposure may therefore help reduce some of the downstream inflammatory effects of overexpressed IRF5 [R].

Both vitamin D and direct sun exposure also seem to increase IL-10, an anti-inflammatory cytokine which is suppressed by IRF5 [R, R, R].

Vitamin D, meanwhile, has been found to improve the symptoms of ulcerative colitis when given as a supplement. Moderate sun exposure is also the best source of vitamin D [R].

Avoid Cigarettes

Some studies showed that smokers tend to have lower IL-10 levels (and higher levels of several inflammatory cytokines) in their blood and saliva. Because IRF5 also suppresses IL-10, cigarette smoke may exacerbate this effect and further increase inflammation [R, R].

Smoking is clearly associated with an increased incidence of Crohn’s disease, while its effects on ulcerative colitis are less evident — this condition seems to be more common among former smokers but less among people who currently smoke [R].

Whether or not you are concerned about your chances of developing IBD, giving up smoking is always a good idea to improve your overall health.

Cigarette smoke may exacerbate the inflammatory effects of IRF5 on the Th1 response and IL-10, while moderate sun exposure may help improve them.

Diet

Mango (Mangiferin)

One of the only natural substances that has consistently been found to reduce IRF5 activity is mangiferin, a polyphenol found in all parts of the mango plant and fruit [R, R].

One clinical trial is available on the effects of mango polyphenols in people with IBD. Of ten IBD patients who consumed mango pulp every day for eight weeks, all experienced a marked improvement in symptoms. The study also found increases in beneficial Lactobacillus species in the patients’ gut flora, suggesting that the mango fiber promoted healthy bacterial remodeling [R].

Mango and its extracts have also been found to reduce inflammation in animal models of ulcerative colitis and IBD [R, R].

Mangiferin, a polyphenol from mango, is among the only natural substances found to directly reduce IRF5.

Fish

Dietary fats are believed to regulate the Th1 immune response, which can be overactivated by high IRF5. In particular, omega-3 fatty acids (like those found in fish and seafood) are the strongest inhibitors of Th1 [R].

High intake of omega-3s from fish may also be protective against the development of IBD [R, R].

Green Tea

EGCG, the main active component of green tea, has been found to suppress the Th1 immune response and increase IL-10, potentially counteracting some of the downstream effects of IRF5 [R, R].

In a small clinical trial on 20 people with ulcerative colitis, a commercial extract with the green tea polyphenol epigallocatechin gallate (Polyphenon E) helped improve the symptoms and maintain remission. Green tea and its polyphenols were similarly effective in multiple studies of animals with colitis [R, R].

Epigallocatechin gallate also improved pouchitis, a complication that may occur in ulcerative colitis patients after the surgical removal of the colon, in a pilot trial on 9 people [R].

Some anti-inflammatory nutrients, including omega-3 fatty acids and EGCG, have been found to reduce inflammation by blocking Th1 and increasing IL-10.

Probiotics

Many beneficial strains of gut bacteria regulate the immune system, suppress the Th1 response, and increase the expression of IL-10, all of which may counteract the downstream effects of high IRF5 [R, R, R].

People with IBD often have impaired gut microbiome, which may worsen their disease. In a meta-analysis, a blended probiotic containing Lactobacillus and Bifidobacterium strains increased remission rates by 1.7 times in ulcerative colitis patients [R].

Lactobacillus and Bifidobacterium strains were beneficial in different trials with ulcerative colitis patients [R, R, R, R].

Improving the composition of the gut flora with probiotic supplements may help suppress the Th1 response and increase IL-10.

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.

More inflammation & autoimmunity blogs

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Content

What is IRF5? IRF5 Variants & Ulcerative Colitis Your IRF5 Results for IBD

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