Intracellular IL-32 regulates mitochondrial metabolism, proliferation, and differentiation of malignant plasma cells

Kristin Roseth Aass, Robin Mjelle, Martin H. Kastnes, Synne S. Tryggestad, Luca M. van den Brink, Ingrid Aass Roseth, Marita Westhrin, Muhammad Zahoor, Siv H. Moen, Tonje M. Vikene Nedal, Glenn Buene, Kristine Misund, Anne-Marit Sponaas, Qianli Ma, Anders Sundan, Richard W. J. Groen, Tobias S. Slørdahl, Anders Waage, Therese Standal*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Interleukin-32 (IL-32) is a nonclassical cytokine expressed in cancers, inflammatory diseases, and infections. Its expression is regulated by two different oxygen sensing systems; HIF1α and cysteamine dioxygenase (ADO), indicating that IL-32 may be involved in the response to hypoxia. We here demonstrate that endogenously expressed, intracellular IL-32 interacts with components of the mitochondrial respiratory chain and promotes oxidative phosphorylation. Knocking out IL-32 in three myeloma cell lines reduced cell survival and proliferation in vitro and in vivo. High-throughput transcriptomic and MS-metabolomic profiling of IL-32 KO cells revealed that cells depleted of IL-32 had perturbations in metabolic pathways, with accumulation of lipids, pyruvate precursors, and citrate. IL-32 was expressed in a subgroup of myeloma patients with inferior survival, and primary myeloma cells expressing IL-32 had a gene signature associated with immaturity, proliferation, and oxidative phosphorylation. In conclusion, we demonstrate a previously unrecognized role of IL-32 in the regulation of plasma cell metabolism.
Original languageEnglish
Article number103605
Issue number1
Publication statusPublished - 21 Jan 2022

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