IL-36 cytokines imprint a colitogenic phenotype on CD4+ T helper cells
IL-36 cytokines are emerging as potent orchestrators of intestinal inflammation and are being implicated in the pathogenesis of inflammatory bowel diseases (IBD). However, the mechanisms through which these cytokines mediate these effects remain to be fully uncovered. Here, we report specifically el...
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| Veröffentlicht in: | Mucosal immunology 2022-03, Vol.15 (3), p.491-503 |
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| creator | Leon, Gemma Hernandez Santana, Yasmina E. Irwin, Naoise Giannoudaki, Eirini O’Neill, Sadhbh Csizmadia, Ilona Gogarty, Martina Lee, Tae J. Ruane, Darren Long, Aideen Fallon, Padraic G. Hussey, Seamus Walsh, Patrick T. |
| description | IL-36 cytokines are emerging as potent orchestrators of intestinal inflammation and are being implicated in the pathogenesis of inflammatory bowel diseases (IBD). However, the mechanisms through which these cytokines mediate these effects remain to be fully uncovered. Here, we report specifically elevated expression of IL-36α, and not IL-36β or IL-36γ in the serum of newly diagnosed, treatment naïve, paediatric IBD patients and identify T cells as primary cellular mediators of IL-36 responses in the inflamed gut. IL-36R expression on CD4
+
T cells was found to promote intestinal pathology in a murine model of colitis. Consistent with these effects, IL-36R can act as a potent instructor of CD4
+
T cell differentiation in vivo, enhancing Th1 responses, while inhibiting the generation of Tregs. In addition, loss of IL-36 responsiveness significantly reduced the migration of pathogenic CD4
+
T cells towards intestinal tissues and IL-36 was found to act, uniquely among IL-1 family members, to induce the expression of gut homing receptors in proinflammatory murine and human CD4
+
T cells. These data reveal an important role for IL-36 cytokines in driving the colitogenic potential of CD4
+
T cells and identify a new mechanism through which they may contribute to disease pathogenesis. |
| doi_str_mv | 10.1038/s41385-022-00488-w |
| format | Article |
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+
T cells was found to promote intestinal pathology in a murine model of colitis. Consistent with these effects, IL-36R can act as a potent instructor of CD4
+
T cell differentiation in vivo, enhancing Th1 responses, while inhibiting the generation of Tregs. In addition, loss of IL-36 responsiveness significantly reduced the migration of pathogenic CD4
+
T cells towards intestinal tissues and IL-36 was found to act, uniquely among IL-1 family members, to induce the expression of gut homing receptors in proinflammatory murine and human CD4
+
T cells. These data reveal an important role for IL-36 cytokines in driving the colitogenic potential of CD4
+
T cells and identify a new mechanism through which they may contribute to disease pathogenesis.</description><identifier>ISSN: 1933-0219</identifier><identifier>EISSN: 1935-3456</identifier><identifier>DOI: 10.1038/s41385-022-00488-w</identifier><identifier>PMID: 35177818</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Allergology ; Animal models ; Animals ; Antibodies ; Biomedical and Life Sciences ; Biomedicine ; CD4 antigen ; Cell differentiation ; Child ; Colitis ; Colitis - metabolism ; Cytokines ; Cytokines - metabolism ; Digestive system ; Gastroenterology ; Gastrointestinal tract ; Helper cells ; Homing behavior ; Homing receptors ; Humans ; Immunology ; Inflammatory bowel diseases ; Inflammatory Bowel Diseases - metabolism ; Interleukin 1 ; Interleukins - immunology ; Intestine ; Lymphocytes ; Lymphocytes T ; Mice ; Pathogenesis ; Phenotype ; Phenotypes ; T-Lymphocytes, Helper-Inducer - metabolism</subject><ispartof>Mucosal immunology, 2022-03, Vol.15 (3), p.491-503</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/. (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-9b79f16d8840dee35c070c9ea9d43e0b57a1330caac833a0b0320fe8a1d2c2c53</citedby><cites>FETCH-LOGICAL-c502t-9b79f16d8840dee35c070c9ea9d43e0b57a1330caac833a0b0320fe8a1d2c2c53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35177818$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leon, Gemma</creatorcontrib><creatorcontrib>Hernandez Santana, Yasmina E.</creatorcontrib><creatorcontrib>Irwin, Naoise</creatorcontrib><creatorcontrib>Giannoudaki, Eirini</creatorcontrib><creatorcontrib>O’Neill, Sadhbh</creatorcontrib><creatorcontrib>Csizmadia, Ilona</creatorcontrib><creatorcontrib>Gogarty, Martina</creatorcontrib><creatorcontrib>Lee, Tae J.</creatorcontrib><creatorcontrib>Ruane, Darren</creatorcontrib><creatorcontrib>Long, Aideen</creatorcontrib><creatorcontrib>Fallon, Padraic G.</creatorcontrib><creatorcontrib>Hussey, Seamus</creatorcontrib><creatorcontrib>Walsh, Patrick T.</creatorcontrib><title>IL-36 cytokines imprint a colitogenic phenotype on CD4+ T helper cells</title><title>Mucosal immunology</title><addtitle>Mucosal Immunol</addtitle><addtitle>Mucosal Immunol</addtitle><description>IL-36 cytokines are emerging as potent orchestrators of intestinal inflammation and are being implicated in the pathogenesis of inflammatory bowel diseases (IBD). However, the mechanisms through which these cytokines mediate these effects remain to be fully uncovered. Here, we report specifically elevated expression of IL-36α, and not IL-36β or IL-36γ in the serum of newly diagnosed, treatment naïve, paediatric IBD patients and identify T cells as primary cellular mediators of IL-36 responses in the inflamed gut. IL-36R expression on CD4
+
T cells was found to promote intestinal pathology in a murine model of colitis. Consistent with these effects, IL-36R can act as a potent instructor of CD4
+
T cell differentiation in vivo, enhancing Th1 responses, while inhibiting the generation of Tregs. In addition, loss of IL-36 responsiveness significantly reduced the migration of pathogenic CD4
+
T cells towards intestinal tissues and IL-36 was found to act, uniquely among IL-1 family members, to induce the expression of gut homing receptors in proinflammatory murine and human CD4
+
T cells. These data reveal an important role for IL-36 cytokines in driving the colitogenic potential of CD4
+
T cells and identify a new mechanism through which they may contribute to disease pathogenesis.</description><subject>Allergology</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>CD4 antigen</subject><subject>Cell differentiation</subject><subject>Child</subject><subject>Colitis</subject><subject>Colitis - metabolism</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Digestive system</subject><subject>Gastroenterology</subject><subject>Gastrointestinal tract</subject><subject>Helper cells</subject><subject>Homing behavior</subject><subject>Homing receptors</subject><subject>Humans</subject><subject>Immunology</subject><subject>Inflammatory bowel diseases</subject><subject>Inflammatory Bowel Diseases - metabolism</subject><subject>Interleukin 1</subject><subject>Interleukins - immunology</subject><subject>Intestine</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Pathogenesis</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>T-Lymphocytes, Helper-Inducer - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Mucosal immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leon, Gemma</au><au>Hernandez Santana, Yasmina E.</au><au>Irwin, Naoise</au><au>Giannoudaki, Eirini</au><au>O’Neill, Sadhbh</au><au>Csizmadia, Ilona</au><au>Gogarty, Martina</au><au>Lee, Tae J.</au><au>Ruane, Darren</au><au>Long, Aideen</au><au>Fallon, Padraic G.</au><au>Hussey, Seamus</au><au>Walsh, Patrick T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-36 cytokines imprint a colitogenic phenotype on CD4+ T helper cells</atitle><jtitle>Mucosal immunology</jtitle><stitle>Mucosal Immunol</stitle><addtitle>Mucosal Immunol</addtitle><date>2022-03-01</date><risdate>2022</risdate><volume>15</volume><issue>3</issue><spage>491</spage><epage>503</epage><pages>491-503</pages><issn>1933-0219</issn><eissn>1935-3456</eissn><abstract>IL-36 cytokines are emerging as potent orchestrators of intestinal inflammation and are being implicated in the pathogenesis of inflammatory bowel diseases (IBD). However, the mechanisms through which these cytokines mediate these effects remain to be fully uncovered. Here, we report specifically elevated expression of IL-36α, and not IL-36β or IL-36γ in the serum of newly diagnosed, treatment naïve, paediatric IBD patients and identify T cells as primary cellular mediators of IL-36 responses in the inflamed gut. IL-36R expression on CD4
+
T cells was found to promote intestinal pathology in a murine model of colitis. Consistent with these effects, IL-36R can act as a potent instructor of CD4
+
T cell differentiation in vivo, enhancing Th1 responses, while inhibiting the generation of Tregs. In addition, loss of IL-36 responsiveness significantly reduced the migration of pathogenic CD4
+
T cells towards intestinal tissues and IL-36 was found to act, uniquely among IL-1 family members, to induce the expression of gut homing receptors in proinflammatory murine and human CD4
+
T cells. These data reveal an important role for IL-36 cytokines in driving the colitogenic potential of CD4
+
T cells and identify a new mechanism through which they may contribute to disease pathogenesis.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>35177818</pmid><doi>10.1038/s41385-022-00488-w</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Allergology Animal models Animals Antibodies Biomedical and Life Sciences Biomedicine CD4 antigen Cell differentiation Child Colitis Colitis - metabolism Cytokines Cytokines - metabolism Digestive system Gastroenterology Gastrointestinal tract Helper cells Homing behavior Homing receptors Humans Immunology Inflammatory bowel diseases Inflammatory Bowel Diseases - metabolism Interleukin 1 Interleukins - immunology Intestine Lymphocytes Lymphocytes T Mice Pathogenesis Phenotype Phenotypes T-Lymphocytes, Helper-Inducer - metabolism |
| title | IL-36 cytokines imprint a colitogenic phenotype on CD4+ T helper cells |
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