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
Hauptverfasser: 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.
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container_end_page eadg6874
container_issue 43
container_start_page eadg6874
container_title Science advances
container_volume 9
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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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. 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subjects Biochemistry
Biomedicine and Life Sciences
Immunology
SciAdv r-articles
title Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions
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