{"id":9119,"date":"2017-11-08T08:27:28","date_gmt":"2017-11-08T07:27:28","guid":{"rendered":"http:\/\/www.wjst.de\/blog\/?p=9119"},"modified":"2017-11-23T12:49:41","modified_gmt":"2017-11-23T11:49:41","slug":"an-update-of-il2-function","status":"publish","type":"post","link":"https:\/\/www.wjst.de\/blog\/sciencesurf\/2017\/11\/an-update-of-il2-function\/","title":{"rendered":"An update of IL2 function"},"content":{"rendered":"

More than 7 years ago, I wrote a blog post that there is nothing new under the sun<\/a> predicting the next asthma genetics study for 2020 to include 100K asthmatics.<\/p>\n

Ok, I am wrong the paper<\/a> appeared already a week ago with 360K \u00a0asthmatics while basically doubling the number to 136 independent risk variants.\u00a0It’s not an asthma only study as the authors had a rather loose definition of asthma or rhinitis or eczema – is is more about the allergy\/atopy complex.<\/p>\n

It will be a long time reading and replicating the data while my first interest was to examine the affected gene list as shown in table ST15. Using the online Enrichr database<\/a> I get the following result from the GO ontology<\/p>\n

\"\"<\/a>
This is basically the same result as the authors see in their table ST20.<\/figcaption><\/figure>\n

 <\/p>\n

The highest combined score is with a negative regulation of IL-2. What does that mean? A genetically disturbed pathway predicted by a gene ontology network?<\/p>\n

IL2 was discovered in 1976 by Robert Gallo<\/a> by growing T-cells in culture for more than nine months by stimulating lymphocytes with phytohemagglutinin. ((IL1 was described back in 1972 by Charles Dinarello<\/a>). Gallo identified T-cell growth factor (TCFG), now known as interleukin-2 (IL-2) as being absolutely important for a protective immune responses (Science 1976<\/a>).<\/p>\n

The next important paper was also published \u00a0in Science 1984<\/a> showing the following figure<\/p>\n

\"\"<\/a><\/p>\n

 <\/p>\n

So we have in allergy 2 hits on IL2: by genetics (as show in the new study) and by early vitamin D supplementation\u00a0(as I reviewed earlier).\u00a0Maybe we need more clinical studies like the\u00a0Zhang 2016<\/a>\u00a0study:<\/p>\n

In a general population-derived birth cohort, we found that in infants who developed food allergy, cord blood displayed a higher monocyte to CD4(+) T cell ratio and a lower proportion of natural regulatory T cell (nT(reg)) in relation to duration of labor. CD14(+) monocytes of food-allergic infants secreted higher amounts of inflammatory cytokines (IL-1\u03b2, IL-6, and tumor necrosis factor-\u03b1) in response to lipopolysaccharide. In the presence of the mucosal cytokine transforming growth factor-\u03b2, these inflammatory cytokines suppressed IL-2 expression by CD4(+) T cells. In the absence of IL-2, inflammatory cytokines decreased the number of activated nT(reg) and diverted the differentiation of both nT(reg) and na\u00efve CD4(+) T cells toward an IL-4-expressing nonclassical TH2 phenotype.<\/p><\/blockquote>\n

Suppressed IL2 is a key for allergy development shown also in experiments by Bonnet 2016<\/a>:<\/p>\n

We previously demonstrated that Tregs can be selectively expanded and activated by low doses of IL-2 (ld-IL-2) inducing immunoregulation without immunosuppression and established its protective effect in autoimmune diseases. In this study, we evaluated the ability of ld-IL-2 to control allergy in an experimental model of food allergy. Ld-IL-2 induced Treg expansion and activation that elicited protection against clinical manifestations of food allergy in two mouse models with OVA and peanut. This clinical effect was lost in Treg-depleted mice, demonstrating the major contribution of Tregs in ld-IL-2 efficacy. Mechanistic studies further indicated that protection from allergy could be explained by a Treg-dependent local modification of the Th1\/Th2 balance and an inhibition of mast cell recruitment and activation. Preventive and therapeutic effects of ld-IL-2 were observed over a 7-mo-period, highlighting its long-term efficacy. This study demonstrated that ld-IL-2 is efficient to prevent and to treat allergic immune responses, and thus represents a promising therapeutic strategy for managing allergic diseases.<\/p><\/blockquote>\n

What we do need now for allergy prevention is a trials of newborns with low dose IL2<\/a> and also more trials refining the IL2 antagonist application of vitamin D.<\/p>\n\n

 <\/p>\n

\n CC-BY-NC Science Surf , accessed 20.04.2026<\/span>\n <\/div>","protected":false},"excerpt":{"rendered":"

More than 7 years ago, I wrote a blog post that there is nothing new under the sun predicting the next asthma genetics study for 2020 to include 100K asthmatics. Ok, I am wrong the paper appeared already a week ago with 360K \u00a0asthmatics while basically doubling the number to 136 independent risk variants.\u00a0It’s not … Continue reading An update of IL2 function<\/span> →<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[8,2],"tags":[],"class_list":["post-9119","post","type-post","status-publish","format-standard","hentry","category-asthma-allergy","category-genetics-biology"],"_links":{"self":[{"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/posts\/9119","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/comments?post=9119"}],"version-history":[{"count":14,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/posts\/9119\/revisions"}],"predecessor-version":[{"id":9175,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/posts\/9119\/revisions\/9175"}],"wp:attachment":[{"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/media?parent=9119"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/categories?post=9119"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.wjst.de\/blog\/wp-json\/wp\/v2\/tags?post=9119"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}