Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions
Interleukins are secreted proteins that regulate immune responses. Among these, the interleukin 12 (IL-12) family holds a central position in inflammatory and infectious diseases. Each family member consists of an α and a β subunit that together form a composite cytokine. Within the IL-12 family, IL...
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Veröffentlicht in: | Science advances 2023-10, Vol.9 (43), p.eadg6874-eadg6874 |
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creator | Hildenbrand, Karen Bohnacker, Sina Menon, Priyanka Rajeev Kerle, Anna Prodjinotho, Ulrich F. Hartung, Franziska Strasser, Patrick C. Catici, Dragana A. M. Rührnößl, Florian Haslbeck, Martin Schumann, Kathrin Müller, Stephanie I. da Costa, Clarissa Prazeres Esser-von Bieren, Julia Feige, Matthias J. |
description | Interleukins are secreted proteins that regulate immune responses. Among these, the interleukin 12 (IL-12) family holds a central position in inflammatory and infectious diseases. Each family member consists of an α and a β subunit that together form a composite cytokine. Within the IL-12 family, IL-35 remains particularly ill-characterized on a molecular level despite its key role in autoimmune diseases and cancer. Here we show that both IL-35 subunits, IL-12α and EBI3, mutually promote their secretion from cells but are not necessarily secreted as a heterodimer. Our data demonstrate that IL-12α and EBI3 are stable proteins in isolation that act as anti-inflammatory molecules. Both reduce secretion of proinflammatory cytokines and induce the development of regulatory T cells. Together, our study reveals IL-12α and EBI3, the subunits of IL-35, to be functionally active anti-inflammatory immune molecules on their own. This extends our understanding of the human cytokine repertoire as a basis for immunotherapeutic approaches.
The human cytokine repertoire has more members than previously thought which limit inflammatory responses. |
doi_str_mv | 10.1126/sciadv.adg6874 |
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The human cytokine repertoire has more members than previously thought which limit inflammatory responses.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.adg6874</identifier><language>eng</language><publisher>American Association for the Advancement of Science</publisher><subject>Biochemistry ; Biomedicine and Life Sciences ; Immunology ; SciAdv r-articles</subject><ispartof>Science advances, 2023-10, Vol.9 (43), p.eadg6874-eadg6874</ispartof><rights>Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). 2023 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c368t-718565d93e6fe2611690f9020a66fbfe701519f5115a548453f1bcc12d783a283</citedby><cites>FETCH-LOGICAL-c368t-718565d93e6fe2611690f9020a66fbfe701519f5115a548453f1bcc12d783a283</cites><orcidid>0000-0002-3063-0949 ; 0000-0002-5337-0406 ; 0000-0001-6709-1240 ; 0000-0002-3851-706X ; 0000-0002-8804-7238 ; 0000-0002-0993-3910 ; 0000-0003-1898-9382 ; 0009-0003-1202-3381 ; 0000-0001-9541-7180 ; 0000-0003-0494-9152 ; 0000-0001-5435-4312</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599630/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599630/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids></links><search><creatorcontrib>Hildenbrand, Karen</creatorcontrib><creatorcontrib>Bohnacker, Sina</creatorcontrib><creatorcontrib>Menon, Priyanka Rajeev</creatorcontrib><creatorcontrib>Kerle, Anna</creatorcontrib><creatorcontrib>Prodjinotho, Ulrich F.</creatorcontrib><creatorcontrib>Hartung, Franziska</creatorcontrib><creatorcontrib>Strasser, Patrick C.</creatorcontrib><creatorcontrib>Catici, Dragana A. M.</creatorcontrib><creatorcontrib>Rührnößl, Florian</creatorcontrib><creatorcontrib>Haslbeck, Martin</creatorcontrib><creatorcontrib>Schumann, Kathrin</creatorcontrib><creatorcontrib>Müller, Stephanie I.</creatorcontrib><creatorcontrib>da Costa, Clarissa Prazeres</creatorcontrib><creatorcontrib>Esser-von Bieren, Julia</creatorcontrib><creatorcontrib>Feige, Matthias J.</creatorcontrib><title>Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions</title><title>Science advances</title><description>Interleukins are secreted proteins that regulate immune responses. Among these, the interleukin 12 (IL-12) family holds a central position in inflammatory and infectious diseases. Each family member consists of an α and a β subunit that together form a composite cytokine. Within the IL-12 family, IL-35 remains particularly ill-characterized on a molecular level despite its key role in autoimmune diseases and cancer. Here we show that both IL-35 subunits, IL-12α and EBI3, mutually promote their secretion from cells but are not necessarily secreted as a heterodimer. Our data demonstrate that IL-12α and EBI3 are stable proteins in isolation that act as anti-inflammatory molecules. Both reduce secretion of proinflammatory cytokines and induce the development of regulatory T cells. Together, our study reveals IL-12α and EBI3, the subunits of IL-35, to be functionally active anti-inflammatory immune molecules on their own. This extends our understanding of the human cytokine repertoire as a basis for immunotherapeutic approaches.
The human cytokine repertoire has more members than previously thought which limit inflammatory responses.</description><subject>Biochemistry</subject><subject>Biomedicine and Life Sciences</subject><subject>Immunology</subject><subject>SciAdv r-articles</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNpVkEFLAzEUhIMoWGqvnvfoZWte0mR3T6Kl2kLRi55Dmk3a6G5Sk2ylP8s_4m9ypUX09Aa-Yd4wCF0CHgMQfh2VlfVuLOs1L4vJCRoQWrCcsEl5-kefo1GMrxhjmHDOoBqgx3nXSpdZl3RodPdmXQ7k6zOTrs5mdwuayaAztU--JzpmHzZtepZsbp1pZNvK5MM-M51TyXoXL9CZkU3Uo-Mdopf72fN0ni-fHhbT22WuKC9TXkDJOKsrqrnRhAPwCpsKEyw5NyujCwx9O8MAmOxrTxg1sFIKSF2UVJKSDtHNIXfbrVpdK-1SkI3YBtvKsBdeWvGfOLsRa78TgFlVcYr7hKtjQvDvnY5JtDYq3TTSad9FQcqSUEIrxnvr-GBVwccYtPn9A1j8rC8O64vj-vQbkDZ7Dg</recordid><startdate>20231027</startdate><enddate>20231027</enddate><creator>Hildenbrand, Karen</creator><creator>Bohnacker, Sina</creator><creator>Menon, Priyanka Rajeev</creator><creator>Kerle, Anna</creator><creator>Prodjinotho, Ulrich F.</creator><creator>Hartung, Franziska</creator><creator>Strasser, Patrick C.</creator><creator>Catici, Dragana A. 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M.</creatorcontrib><creatorcontrib>Rührnößl, Florian</creatorcontrib><creatorcontrib>Haslbeck, Martin</creatorcontrib><creatorcontrib>Schumann, Kathrin</creatorcontrib><creatorcontrib>Müller, Stephanie I.</creatorcontrib><creatorcontrib>da Costa, Clarissa Prazeres</creatorcontrib><creatorcontrib>Esser-von Bieren, Julia</creatorcontrib><creatorcontrib>Feige, Matthias J.</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hildenbrand, Karen</au><au>Bohnacker, Sina</au><au>Menon, Priyanka Rajeev</au><au>Kerle, Anna</au><au>Prodjinotho, Ulrich F.</au><au>Hartung, Franziska</au><au>Strasser, Patrick C.</au><au>Catici, Dragana A. M.</au><au>Rührnößl, Florian</au><au>Haslbeck, Martin</au><au>Schumann, Kathrin</au><au>Müller, Stephanie I.</au><au>da Costa, Clarissa Prazeres</au><au>Esser-von Bieren, Julia</au><au>Feige, Matthias J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions</atitle><jtitle>Science advances</jtitle><date>2023-10-27</date><risdate>2023</risdate><volume>9</volume><issue>43</issue><spage>eadg6874</spage><epage>eadg6874</epage><pages>eadg6874-eadg6874</pages><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>Interleukins are secreted proteins that regulate immune responses. Among these, the interleukin 12 (IL-12) family holds a central position in inflammatory and infectious diseases. Each family member consists of an α and a β subunit that together form a composite cytokine. Within the IL-12 family, IL-35 remains particularly ill-characterized on a molecular level despite its key role in autoimmune diseases and cancer. Here we show that both IL-35 subunits, IL-12α and EBI3, mutually promote their secretion from cells but are not necessarily secreted as a heterodimer. Our data demonstrate that IL-12α and EBI3 are stable proteins in isolation that act as anti-inflammatory molecules. Both reduce secretion of proinflammatory cytokines and induce the development of regulatory T cells. Together, our study reveals IL-12α and EBI3, the subunits of IL-35, to be functionally active anti-inflammatory immune molecules on their own. This extends our understanding of the human cytokine repertoire as a basis for immunotherapeutic approaches.
The human cytokine repertoire has more members than previously thought which limit inflammatory responses.</abstract><pub>American Association for the Advancement of Science</pub><doi>10.1126/sciadv.adg6874</doi><orcidid>https://orcid.org/0000-0002-3063-0949</orcidid><orcidid>https://orcid.org/0000-0002-5337-0406</orcidid><orcidid>https://orcid.org/0000-0001-6709-1240</orcidid><orcidid>https://orcid.org/0000-0002-3851-706X</orcidid><orcidid>https://orcid.org/0000-0002-8804-7238</orcidid><orcidid>https://orcid.org/0000-0002-0993-3910</orcidid><orcidid>https://orcid.org/0000-0003-1898-9382</orcidid><orcidid>https://orcid.org/0009-0003-1202-3381</orcidid><orcidid>https://orcid.org/0000-0001-9541-7180</orcidid><orcidid>https://orcid.org/0000-0003-0494-9152</orcidid><orcidid>https://orcid.org/0000-0001-5435-4312</orcidid><oa>free_for_read</oa></addata></record> |
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title | Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions |
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