The role of Optineurin in innate immunity and inflammatory diseases

A study on optineurin explores its multifaceted roles in cellular functions and its links to immune dysfunction in various diseases.

Andrew Smith, Gregory Sebepos-Rogers, David Sanders, Abdulaziz Ghannam

The multifunctional adaptor optineurin has been implicated in whole host of protein-protein interactions and cellular functions, for example, as an adaptor during inflammatory signalling, autophagy, and vesicle trafficking.

The interest in optineurin intensified after the identification of various mutations and polymorphisms in several human diseases, including primary open-angle glaucoma, amyotrophic lateral sclerosis and Paget's disease of the bone. With their distinct pathogenesis these diseases at first seem unrelated, but emerging evidence points to an immune disfunction as a common aetiology.

Our group conducted a transcriptomic analysis of immune cells from patients with Crohn’s disease and identified optineurin as the most under expressed gene within this population (Immunology 2015). Subsequent mechanistic studies have demonstrated that the loss in optineurin can result in increased susceptibility to bacterial infection and the development of chronic bowel inflammation (Dis Model Mech 2015 and JEM 2017). More recently our work has focused on how optineurin regulates the immune response and identified a role for this molecule in antiviral immune regulation (J Cell Sci 2020).

Current activities

We are currently expanding our research into optineurin in regards to its role in intestinal epithelial cell immune regulation and how autophagy controls inflammation. We are also interested in understanding how optineurin is regulated by the innate immune system and how these processed become dysregulated in a number of inflammatory diseases, such as Crohn’s Disease, primary open-angle glaucoma and amyotrophic lateral sclerosis.