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Hildenbrand, K.* ; Bohnacker, S. ; Menon, P.R.* ; Kerle, A.* ; Prodjinotho, U.F.* ; Hartung, F. ; Strasser, P.C.* ; Catici, D.A.M.* ; Rührnößl, F.* ; Haslbeck, M.* ; Schumann, K.* ; Müller, S.I.* ; da Costa, C.P.* ; Esser-von Bieren, J. ; Feige, M.J.*

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

Sci. Adv. 9:eadg6874 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Regulatory B-cells; Induced Gene 3; Il-35; Receptor; Il-12; Promotes; Subunit; Protein; Il-23; Expression
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Journal Science Advances
Quellenangaben Volume: 9, Issue: 43, Pages: , Article Number: eadg6874 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Allergy Research (IAF)
Grants Helmholtz Young Investigator grant
DFG
Studienstiftung des deutschen Volkes PhD scholarship
Cusanuswerk PhD scholarship