192 | id == 192
192 | category_id == 16
192 | category_order == 13
192 | category_name == Gut Health
192 | category_color == #C47AC0
192 | slug == IRF5-IBD
192 | title == How Does This Gene Stimulate Th1 and Promote IBD? (IRF5)
192 | meta_description == IRF5 stimulates the Th1 response, suppresses IL-10, and may promote the development of ulcerative colitis. Learn more here.
192 | summary == <p><strong>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.</strong></p>
192 | overall_score_text == Gut Inflammation Score (based on IRF5)
192 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/IRF5--Gut-Inflammation-IBD---all-chips.jpg
192 | author_id == 1
192 | author_name == Jasmine Foster
192 | author_title == BSc, BEd
192 | author_order == 36
192 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Jasmine.jpg
192 | author_intro == <p><strong>Jasmine received her BS from McGill University and her BEd from Vancouver Island University.</strong></p>    <p>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.</p>
192 | reviewer == None
192 | medical_reviewer_id == 11
192 | medical_reviewer_name == Puya Yazdi
192 | medical_reviewer_title == MD
192 | publish_date == 2020
192 | publish_date == 5
192 | publish_date == 18
192 | avg_rating == 4.0
192 | tags_id == 194
192 | tags_name == Gut Health
192 | tags_id == 308
192 | tags_name == Gut Inflammation
192 | tags_id == 73
192 | tags_name == IBD
192 | tags_id == 240
192 | tags_name == IL-10
192 | tags_id == 447
192 | tags_name == IRF5 Gene
192 | tags_id == 196
192 | tags_name == Ulcerative Colitis
192 | permissions_favorite == False
192 | permissions_rate == False
192 | content_article == <p><em><span style="font-weight: 400;">This article is for informational purposes only. None of the information here should be taken as medical advice. If you suspect you may have digestive issues, seek medical help. </span></em><em><span style="font-weight: 400;">Keep in mind that these results are based on association studies, which are correlative and aren&rsquo;t necessarily causative. Any single genetic variant will typically contribute only a small proportion to the overall risk of the condition, and non-genetic factors play a large role in developing a condition as well. Therefore, just because you have one of these genotypes does not necessarily mean you are at an increased risk of developing this condition!</span></em></p> <h2><span style="font-weight: 400;">What is IRF5?</span></h2> <p><span style="font-weight: 400;">IRF5 (interferon regulatory factor 5) regulates the expression of interferons and promotes </span><a href="http://selfhacked.com/blog/supplements-people-th1-dominant/"><span style="font-weight: 400;">Th1</span></a><span style="font-weight: 400;"> and </span><a href="http://selfhacked.com/blog/th17/"><span style="font-weight: 400;">Th17</span></a><span style="font-weight: 400;"> inflammatory responses. Macrophages, a type of </span><a href="https://selfhacked.com/blog/how-to-increase-and-decrease-white-blood-cells/"><span style="font-weight: 400;">white blood cell</span></a><span style="font-weight: 400;"> 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 </span><a href="http://selfhacked.com/blog/il-10/"><span style="font-weight: 400;">IL-10</span></a><span style="font-weight: 400;"> [</span><a href="https://www.nature.com/articles/ni.1990"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">IRF5 has, unsurprisingly, been implicated in a variety of inflammatory diseases, including cancer, lupus erythematosus, and ulcerative colitis [</span><a href="https://www.nature.com/articles/ni.1990"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://academic.oup.com/intimm/article/30/11/529/5026002"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/26192919"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">What is Ulcerative Colitis?</span></h3> <p><span style="font-weight: 400;">IBD is a group of autoimmune diseases characterized by inflammation and sores in the gut lining, which can result in diarrhea, abdominal </span><a href="https://selfhacked.com/blog/23-ways-to-combat-pain-naturally-by-increasing-your-opioids/"><span style="font-weight: 400;">pain</span></a><span style="font-weight: 400;">, fatigue, fever, rectal bleeding, nutritional deficiencies, and </span><a href="http://selfhacked.com/blog/a-comprehensive-list-of-effective-ways-to-lose-weight/"><span style="font-weight: 400;">weight loss</span></a><span style="font-weight: 400;">. The definition of IBD includes both ulcerative colitis and Crohn&rsquo;s disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980998/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Ulcerative colitis (UC) differs from Crohn&rsquo;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&rsquo;s can damage much broader swaths of tissue [</span><a href="https://www.niddk.nih.gov/health-information/digestive-diseases/ulcerative-colitis"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.niddk.nih.gov/health-information/digestive-diseases/crohns-disease/definition-facts"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/books/NBK459282/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><span style="font-weight: 400;">IRF5 in Inflammatory Disease</span></h3> <p><span style="font-weight: 400;">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 [</span><a href="https://www.nature.com/articles/ni.1990"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">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 [</span><a href="https://www.nature.com/articles/s41575-019-0172-4"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098861/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Inhibiting IRF5 has been proposed as a potential drug target for diseases, including IBD, in which macrophages may be responsible for excessive inflammation [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563445/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">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.</span></p> <h2><span style="font-weight: 400;">IRF5 Variants &amp; Ulcerative Colitis</span></h2> <p><span style="font-weight: 400;">At least one IRF5 variant, rs4728142,&nbsp; has been linked to ulcerative colitis. At this SNP, the uncommon &lsquo;A&rsquo; allele is associated with increased inflammation and rates of disease [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084597/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The risk allele&rsquo;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 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829354/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.jimmunol.org/content/200/1_Supplement/45.6"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">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 [</span><a href="https://www.nature.com/articles/ni.1990"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">At rs4728142, the &lsquo;A&rsquo; allele is associated with increased rates of ulcerative colitis. This variant very likely causes increased expression or activity of IRF5.</span></p> <h2><span style="font-weight: 400;">Your IRF5 Results for IBD</span></h2> <p><em><span style="font-weight: 400;">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.</span></em></p> <p>*2184594355520945*</p> <h3><span style="font-weight: 400;">SNP Summary and Table</span></h3> <p><strong>IRF5 rs4728142</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Not associated with ulcerative colitis</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Associated with ulcerative colitis; likely to increase IRF5 expression and suppress IL-10</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">About half of all people worldwide have at least one copy of the &lsquo;A&rsquo; allele.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;A&rsquo; 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%).</span></li> </ul> <p>*8863909362689792*</p> <h2><span style="font-weight: 400;">Recommendations for Reducing Gut Inflammation</span></h2> <p>*1139924406779870*</p> <p><em><span style="font-weight: 400;">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.</span></em></p> <h3><span style="font-weight: 400;">Lifestyle</span></h3> <h4><span style="font-weight: 400;">Moderate Sun Exposure</span></h4> <p><span style="font-weight: 400;">Exposure to UVB rays has been found to inhibit the Th1 immune response, which is activated by IRF5. Moderate </span><a href="https://selfhacked.com/blog/avoiding-sun-will-kill-14-proven-science-based-health-benefits-sun/"><span style="font-weight: 400;">sun exposure</span></a><span style="font-weight: 400;"> may therefore help reduce some of the downstream inflammatory effects of overexpressed IRF5 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2326852/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Both </span><a href="http://selfhacked.com/blog/35proven-health-benefits-vitamin-d-part-1/"><span style="font-weight: 400;">vitamin D</span></a><span style="font-weight: 400;"> and direct sun exposure also seem to increase IL-10, an anti-inflammatory cytokine which is suppressed by IRF5 [</span><a href="https://nutritionj.biomedcentral.com/articles/10.1186/s12937-019-0507-6"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/17848808"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2326852/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">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 [</span><a href="https://nutritionj.biomedcentral.com/articles/10.1186/s12937-019-0441-7"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><span style="font-weight: 400;">Avoid Cigarettes</span></h4> <p><span style="font-weight: 400;">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 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266915/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29243879"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Smoking is clearly associated with an increased incidence of Crohn&rsquo;s disease, while its effects on ulcerative colitis are less evident &mdash; this condition seems to be more common among former smokers but less among people who currently smoke [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17120402"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">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.</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Cigarette smoke may exacerbate the inflammatory effects of IRF5 on the Th1 response and IL-10, while moderate sun exposure may help improve them.</span></p> <h3><span style="font-weight: 400;">Diet</span></h3> <h4><span style="font-weight: 400;">Mango (Mangiferin)</span></h4> <p><span style="font-weight: 400;">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 [</span><a href="https://www.frontiersin.org/articles/10.3389/fimmu.2018.02622/full"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/27277156"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">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 </span><em><span style="font-weight: 400;">Lactobacillus</span></em><span style="font-weight: 400;"> species in the patients&rsquo; gut flora, suggesting that the mango fiber promoted healthy bacterial remodeling [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/32109839"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Mango and its extracts have also been found to reduce inflammation in animal models of ulcerative colitis and IBD [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053910/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452255/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Mangiferin, a polyphenol from mango, is among the only natural substances found to directly reduce IRF5.</span></p> <h4><span style="font-weight: 400;">Fish</span></h4> <p><span style="font-weight: 400;">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 [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11261793"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">High intake of </span><a href="http://selfhacked.com/blog/top-22-science-based-health-benefits-of-fish-oil/"><span style="font-weight: 400;">omega-3s</span></a><span style="font-weight: 400;"> from fish may also be protective against the development of IBD [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29543869"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153885/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><span style="font-weight: 400;">Green Tea</span></h4> <p><a href="https://selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">EGCG</span></a><span style="font-weight: 400;">, 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 [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23064699"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20175943"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a small clinical trial on 20 people with ulcerative colitis, a commercial extract with the </span><a href="https://selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">green tea</span></a><span style="font-weight: 400;"> 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 [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23846486"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30935522"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">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 [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28929216"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Some anti-inflammatory nutrients, including omega-3 fatty acids and EGCG, have been found to reduce inflammation by blocking Th1 and increasing IL-10.</span></p> <h3><span style="font-weight: 400;">Probiotics</span></h3> <p><span style="font-weight: 400;">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 [</span><a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047244"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20548777"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168568/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">People with IBD often have impaired </span><a href="https://www.selfhacked.com/blog/gut-bacteria-microbiome/"><span style="font-weight: 400;">gut microbiome</span></a><span style="font-weight: 400;">, which may worsen their disease. In a meta-analysis, a blended </span><a href="https://selfhacked.com/blog/probiotics-good-bacteria/"><span style="font-weight: 400;">probiotic</span></a><span style="font-weight: 400;"> containing </span><a href="https://selfhacked.com/blog/l-plantarum/"><em><span style="font-weight: 400;">Lactobacillus</span></em></a> <span style="font-weight: 400;">and </span><a href="https://selfhacked.com/blog/b-longum/"><em><span style="font-weight: 400;">Bifidobacterium</span></em></a> <span style="font-weight: 400;">strains increased remission rates by 1.7 times in ulcerative colitis patients [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24280877"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><em><span style="font-weight: 400;">Lactobacillus</span></em><span style="font-weight: 400;"> and </span><em><span style="font-weight: 400;">Bifidobacterium</span></em><span style="font-weight: 400;"> strains were beneficial in different trials with ulcerative colitis patients [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24280877"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15507864"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15984978"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19174792"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Improving the composition of the gut flora with probiotic supplements may help suppress the Th1 response and increase IL-10.</span></p>
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192 | content_learn_more_8863909362689792_text == Based on the variants we looked at, your IRF5 gene is associated with roughly average rates of ulcerative colitis. However, this doesn't necessarily reflect your overall risk of ulcerative colitis, just one gene related to it. Mango, omega-3 fatty acids, and other anti-inflammatory strategies may help; read on to learn more.
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rsIDs = rs4728142
rsStatus = rs4728142,,chr7,128933913,G,A,,,16,7,HET
