TY - JOUR
T1 - Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions
AU - Hildenbrand, Karen
AU - Bohnacker, Sina
AU - Menon, Priyanka Rajeev
AU - Kerle, Anna
AU - Prodjinotho, Ulrich F.
AU - Hartung, Franziska
AU - Strasser, Patrick C.
AU - Catici, Dragana A.M.
AU - Ruhrnosl, Florian
AU - Haslbeck, Martin
AU - Schumann, Kathrin
AU - Muller, Stephanie I.
AU - da Costa, Clarissa Prazeres
AU - Esser-Von Bieren, Julia
AU - Feige, Matthias J.
N1 - Publisher Copyright:
© 2023 The Authors.
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85175218177&partnerID=8YFLogxK
U2 - 10.1126/sciadv.adg6874
DO - 10.1126/sciadv.adg6874
M3 - Article
C2 - 37878703
AN - SCOPUS:85175218177
SN - 2375-2548
VL - 9
JO - Science Advances
JF - Science Advances
IS - 43
M1 - eadg6874
ER -
