Biogenesis and engineering of interleukin 12 family cytokines

• Published in: Trends in biochemical sciences (Amsterdam. Regular ed.) 2022-11, Vol.47 (11), p.936-949
• Main Authors: Hildenbrand, Karen, Aschenbrenner, Isabel, Franke, Fabian C., Devergne, Odile, Feige, Matthias J.
• Format: Article
• Language: English
• Subjects: chaperones; endoplasmic reticulum quality control; heterodimeric cytokines; interleukin structure; Life Sciences; protein engineering; subunit sharing
• ISSN: 0968-0004; 1362-4326; 0968-0004
• DOI: 10.1016/j.tibs.2022.05.005

Interleukin 12 (IL-12) family cytokines are secreted proteins that regulate immune responses. Each family member is a heterodimer and nature uses shared building blocks to assemble the functionally distinct IL-12 cytokines. In recent years we have gained insights into the molecular principles and cellular regulation of IL-12 family biogenesis. For each of the family members, generally one subunit depends on its partner to acquire its native structure and be secreted from immune cells. If unpaired, molecular chaperones retain these subunits in cells. This allows cells to regulate and control secretion of the highly potent IL-12 family cytokines. Molecular insights gained into IL-12 family biogenesis, structure, and function now allow us to engineer IL-12 family cytokines to develop novel immunotherapeutic approaches. Interleukin 12 (IL-12) family cytokines connect innate and adaptive immunity and are key signaling molecules in the immune system.Nature uses shared building blocks to assemble the functionally distinct family members.In recent years, we have gained detailed mechanistic insights into IL-12 cytokine biogenesis on the transcriptional, translational, and post-translational level, as well as structural insights into receptor binding.Currently, IL-12 family members are (re-)emerging as very attractive molecules for immunotherapeutic approaches.