Loss of the USP18 Gene Causes Tissue Specific Increases in Free and Conjugated ISG15

Hosseini-Joujili, Mohammad; Bikorimana, Emmanuel; Sidebotham, Nicole A.

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https://hdl.handle.net/2142/99866 Copy

Description

Title

Loss of the USP18 Gene Causes Tissue Specific Increases in Free and Conjugated ISG15

Author(s)

• Hosseini-Joujili, Mohammad
• Bikorimana, Emmanuel
• Sidebotham, Nicole A.

Contributor(s)

Freemantle, Sarah

Issue Date

2018-04

Keyword(s)

• Comparative Biosciences
• ISG15
• USP18
• Auto-Inflammation
• Autoimmune Disease

Abstract

USP18 (ubiquitin-specific protease 18) is a dual function protein. It removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins and it inhibits the activity of the interferon receptor by interacting with IFNAR2. We determined that FVB mice lacking USP18 have extensive immune infiltration in their brown adipose tissue. These mice are also cold intolerant which is suggestive of a defect in brown adipose function. We wanted to determine if the levels of both conjugated and non-conjugated ISG15 differed in different tissues of these mice compared to normal animals. Using western analyses, we compared the level of ISG15 in a variety of tissues. Brown adipose tissue showed the highest upregulation of conjugated and unconjugated ISG15. USP18 and ISG15 are part of the innate immune system that is the early pathogen recognition system alerting adjacent cells to imminent attack. USP18 is a negative feedback inhibitor of type I interferon signaling that ensures signaling is turned off after the threat has gone. Inappropriate type I interferon signaling contributes to the development of autoimmunity as has been confirmed in autoimmune diseases including systemic lupus erythematosus and Sjogren’s syndrome. We are currently investigating the potential for brown and white adipose tissue to initiate inappropriate interferon signaling that might contribute to the onset and variable penetrance of autoimmune diseases.

Type of Resource

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http://hdl.handle.net/2142/99866

Copyright and License Information

• Copyright 2018 Mohammad Hosseini-Joujili
• Copyright 2018 Emmanuel Bikorimana
• Copyright 2018 Nicole A. Sidebotham

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