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</div> </div> </nav> <h1 id="firstHeading" class="firstHeading mw-first-heading"><span class="mw-page-title-main">Interleukin 27</span></h1> <div id="p-lang-btn" class="vector-dropdown mw-portlet mw-portlet-lang" > <input type="checkbox" id="p-lang-btn-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-p-lang-btn" class="vector-dropdown-checkbox mw-interlanguage-selector" aria-label="Go to an article in another language. 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.hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">"IL-27" redirects here. For the road, see <a href="/wiki/Illinois_Route_27" class="mw-redirect" title="Illinois Route 27">Illinois Route 27</a>.</div> <p><b>Interleukin 27</b> (IL-27) is a member of the <a href="/wiki/Interleukin_12" title="Interleukin 12">IL-12</a> cytokine family. It is a heterodimeric <a href="/wiki/Cytokine" title="Cytokine">cytokine</a> that is encoded by two distinct genes, <a href="/wiki/EBI3" title="EBI3">Epstein-Barr virus-induced gene 3</a> (EBI3) and IL-27p28. IL-27 is expressed by <a href="/wiki/Antigen-presenting_cell" title="Antigen-presenting cell">antigen presenting cells</a> and interacts with a specific cell-surface receptor complex known as <a href="/wiki/Interleukin-27_receptor" title="Interleukin-27 receptor">IL-27 receptor</a> (IL-27R).<sup id="cite_ref-Yoshida_2015_1-0" class="reference"><a href="#cite_note-Yoshida_2015-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Meka_2015_2-0" class="reference"><a href="#cite_note-Meka_2015-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Yoshimoto_2015_3-0" class="reference"><a href="#cite_note-Yoshimoto_2015-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Iwasaki_2015_4-0" class="reference"><a href="#cite_note-Iwasaki_2015-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Aparicio-Siegmund_2015_5-0" class="reference"><a href="#cite_note-Aparicio-Siegmund_2015-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> This receptor consists of two proteins, IL-27Rɑ and gp130. IL-27 induces differentiation of the diverse populations of T cells in the immune system and also upregulates <a href="/wiki/Interleukin_10" title="Interleukin 10">IL-10</a>. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Signal_transduction">Signal transduction</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Interleukin_27&action=edit&section=1" title="Edit section: Signal transduction"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>When IL-27 binds to the IL-27 receptor, signaling pathways including <a href="/wiki/JAK-STAT_signaling_pathway" title="JAK-STAT signaling pathway">JAK-STAT</a> and p38 MAPK pathways are turned on.<sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Meka_2015_2-1" class="reference"><a href="#cite_note-Meka_2015-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> There are two types of responses, pro-inflammatory and anti-inflammatory, which involve different types of cells, such as <a href="/wiki/Macrophage" title="Macrophage">macrophages</a>, <a href="/wiki/Dendritic_cell" title="Dendritic cell">dendritic cells</a>, <a href="/wiki/T_cell" title="T cell">T cells</a>, and <a href="/wiki/B_cell" title="B cell">B cells</a>.<sup id="cite_ref-Yoshimoto_2015_3-1" class="reference"><a href="#cite_note-Yoshimoto_2015-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> The response that is activated is very much dependent on the external surrounding of IL-27.<sup id="cite_ref-Yoshida_2015_1-1" class="reference"><a href="#cite_note-Yoshida_2015-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Meka_2015_2-2" class="reference"><a href="#cite_note-Meka_2015-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Yoshimoto_2015_3-2" class="reference"><a href="#cite_note-Yoshimoto_2015-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Differentiation_of_T_cells">Differentiation of T cells</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Interleukin_27&action=edit&section=2" title="Edit section: Differentiation of T cells"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>There are many different subsets of T cells, such as Th1, Th2, Th17, <a href="/wiki/Type_1_regulatory_T_cells_(Tr1_cells)" class="mw-redirect" title="Type 1 regulatory T cells (Tr1 cells)">Tr1</a>, and <a href="/wiki/Regulatory_T_cell" title="Regulatory T cell">Treg</a> cells; IL-27 is greatly involved in differentiation through inducing or suppressing of each T cell subset.<sup id="cite_ref-Yoshida_2015_1-2" class="reference"><a href="#cite_note-Yoshida_2015-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Meka_2015_2-3" class="reference"><a href="#cite_note-Meka_2015-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Iwasaki_2015_4-1" class="reference"><a href="#cite_note-Iwasaki_2015-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Aparicio-Siegmund_2015_5-1" class="reference"><a href="#cite_note-Aparicio-Siegmund_2015-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> Th1 cells, which express <a href="/wiki/Interferon_gamma" title="Interferon gamma">IFNγ</a>, are generated by IL-27 through <a href="/wiki/STAT1" title="STAT1">STAT1</a> dimerization and nuclear localization which subsequently leads to the expression of T-bet and signature Th1 genes. Th2 cells, which express <a href="/wiki/Interleukin_4" title="Interleukin 4">IL-4</a>, are inhibited by IL-27 through the transcription factor <a href="/wiki/GATA3" title="GATA3">GATA-3</a>. Th17 cells, which express IL-17, IL-22, and <a href="/wiki/Granulocyte_macrophage_colony-stimulating_factor" class="mw-redirect" title="Granulocyte macrophage colony-stimulating factor">granulocyte macrophage colony-stimulating factor</a> (GM-CSF), are inhibited by IL-27 through STAT1 and expression of transcription factor RORγt. Tr1 cells, which express IL-10, are induced by IL-27 through the transcription factor c-Maf. Treg cells are inhibited by IL-27 through STAT1 and STAT3.<sup id="cite_ref-Meka_2015_2-4" class="reference"><a href="#cite_note-Meka_2015-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Iwasaki_2015_4-2" class="reference"><a href="#cite_note-Iwasaki_2015-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Aparicio-Siegmund_2015_5-2" class="reference"><a href="#cite_note-Aparicio-Siegmund_2015-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="IL-10_production">IL-10 production</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Interleukin_27&action=edit&section=3" title="Edit section: IL-10 production"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>IL-10 acts in an anti-inflammatory manner by suppressing inflammatory responses.<sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> One way that IL-27 can have an anti-inflammatory response is through the expression of IL-10. IL-27 has been found to be involved in the production of IL-10 by stimulating the various subsets of T cells, especially Tr1 cells. Also involved are the STAT1 and <a href="/wiki/STAT3" title="STAT3">STAT3</a> transcription factors that bind specifically to the receptor subunits, IL-27ɑ and glycoprotein. IL-27 is able to activate STAT3 signaling, which eventually leads to an increase of IL-10 secretion from Treg cells.<sup id="cite_ref-Yoshida_2015_1-3" class="reference"><a href="#cite_note-Yoshida_2015-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Interleukin_27&action=edit&section=4" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist"> <div class="mw-references-wrap"><ol class="references"> <li id="cite_note-Yoshida_2015-1"><span class="mw-cite-backlink">^ <a href="#cite_ref-Yoshida_2015_1-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Yoshida_2015_1-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-Yoshida_2015_1-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-Yoshida_2015_1-3"><sup><i><b>d</b></i></sup></a></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px 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