Molecular characterisation of ILRUN, a novel inhibitor of proinflammatory and antimicrobial cytokines

• Main Authors: Rebecca L. Ambrose, Aaron M. Brice, Alessandro T. Caputo, Marina R. Alexander, Leon Tribolet, Yu Chih Liu, Timothy E. Adams, Andrew G.D. Bean, Cameron R. Stewart
• Format: Article
• Language: English
• Published: Elsevier 2020-06-01
• Series: Heliyon
• Subjects: Immunolgy; Inflammation; Infectious disease; Immune response; Viruses; Biochemistry
• Online Access: http://www.sciencedirect.com/science/article/pii/S2405844020309592

Regulation of type-I interferon (IFN) production is essential to the balance between antimicrobial defence and autoimmune disorders. The human protein-coding gene ILRUN (inflammation and lipid regulator with UBA-like and NBR1-like domains, previously C6orf106) was recently characterised as an inhibitor of antiviral and proinflammatory cytokine (interferon-alpha/beta and tumor necrosis factor alpha) transcription. Currently there is a paucity of information about the molecular characteristics of ILRUN, despite it being associated with several diseases including virus infection, coronary artery disease, obesity and cancer. Here, we characterise ILRUN as a highly phylogenetically conserved protein containing UBA-like and a NBR1-like domains that are both essential for inhibition of type-I interferon and tumor necrosis factor alpha) transcription in human cells. We also solved the crystal structure of the NBR1-like domain, providing insights into its potential role in ILRUN function. This study provides critical information for future investigations into the role of ILRUN in health and disease.