The Role of Optineurin in Immunity and Immune-Mediated Diseases

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Background

Optineurin (OPTN) is a ubiquitously expressed, multifunctional adaptor protein associated with a number of major cellular processes and various human diseases. Glaucoma, Amyotrophic Lateral Sclerosis (ALS), Paget’s disease as well as Crohn’s disease have all been linked with abnormalities in OPTN. Specifically, mutations that map to genomic regions encoding functional domains of OPTN have been identified in glaucoma and ALS patients. Furthermore, genome-wide association studies have implicated OPTN in Paget’s disease and transcriptomic studies have linked reduced expression of OPTN in macrophages derived from patients with Crohn’s disease. It seems evident from studies being carried out on OPTN that there are common overlapping pathways and processes associated with these diverse diseases. The growing realization that OPTN plays an active role in the process of selective autophagy of mitochondria (mitophagy) and of protein aggregates (aggrephagy), as well as necroptosis, potentially implicate this multifunctional protein in a variety of additional neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease.

Current evidence also supports a role for OPTN in a number of immune-mediated processes, including (i) defence against cytosolic bacteria via selective autophagy (xenophagy); (ii) intracellular signalling, (iii) cytokine induction and secretion, and (iv) neurodegeneration. Neuroinflammation is one of the earliest and most consistent signs of neurodegeneration, and OPTN deficient mouse model exhibits signs of chronic microglial activation. Moreover, microglia-specific optineurin deletion triggers axonal degeneration. OPTN deficiency also renders animals more susceptible to (i) developing bowel inflammation, (ii) bacterial infection, (iii) reduced Type-I interferon gene induction, and (iv) diminished pro-inflammatory cytokine secretion, thus confirming the essential but complex role this protein plays in the immune response.

We seek Original Research, Review, Mini-Review, Methods, Protocols, Perspective and Hypothesis and Theory articles that cover, but are not limited to, the following topics:

1. Understanding the role of OPTN in the immune system.
2. Identification and characterization of OPTN mutations associated with human disease.
3. Determining the roles of OPTN in neuroinflammation and/or necroptosis.
4. The role of OPTN in selective autophagy.
5. OPTN mediated vesicle trafficking.
6. Development of therapeutic strategies targeting OPTN associated processes.
7. The role of selective ubiquitination in OPTN function.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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