학술논문
Human interleukin-12a and EBI3 are cytokines with anti-inflammatory functions.
Document Type
Article
Author
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.; Prazeres da Costa, Clarissa; Bieren, Julia Esser-von; Feige, Matthias J.
Source
Subject
*REGULATORY T cells
*CYTOKINES
*IMMUNE response
*HETERODIMERS
*AUTOIMMUNE diseases
*INTERLEUKIN-23
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Language
ISSN
2375-2548
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 a and a ß 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-12a and EBI3, mutually promote their secretion from cells but are not necessarily secreted as a heterodimer. Our data demonstrate that IL-12a 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-12a 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. [ABSTRACT FROM AUTHOR]