Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions

Karen Hildenbrand, Sina Bohnacker, Priyanka Rajeev Menon, Anna Kerle, Ulrich F. Prodjinotho, Franziska Hartung, Patrick C. Strasser, Dragana A.M. Catici, Florian Ruhrnosl, Martin Haslbeck, Kathrin Schumann, Stephanie I. Muller, Clarissa Prazeres da Costa, Julia Esser-Von Bieren, Matthias J. Feige

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish
Article numbereadg6874
JournalScience Advances
Issue number43
StatePublished - Oct 2023


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