ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 2093

Glucocorticoid-Induced Leucine Zipper (GILZ) Deficiency Worsens Autoimmunity in the Lyn-Deficient Murine Model of Lupus By Disinhibiting the Type I Interferon (IFN) Pathway

Champa Nataraja1, Eric Morand1, Jacinta Lee1, Taylah Bennett1, Jacqueline Flynn1, James Harris1 and Sarah Jones2, 1Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia, 2School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Auto-immunity, glomerulonephritis and interferons, SLE

  • Tweet
  • Email
  • Print
Session Information

Date: Tuesday, October 23, 2018

Session Title: Systemic Lupus Erythematosus – Animal Models Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease associated with B cell hyperactivity driven by dysregulated type I IFN. Lyn-deficient mice develop lupus-like autoimmunity due to loss of inhibitory regulation of B cell receptor signalling, resulting in hyperactive B cells, excess IL-6 production, and tissue inflammation. Mice deficient in glucocorticoid-induced leucine zipper (GILZ), an intracellular protein involved in glucocorticoid actions, develop lupus-like autoimmunity and excess B cell activation. GILZ is suppressed in human SLE (Jones et al., 2016), but the effects of GILZ in murine models of SLE are unknown. We tested the hypothesis that loss of GILZ exacerbates autoimmunity in the Lyn-deficient murine model of lupus.

Methods: We crossed GILZ-deficient mice onto a Lyn-deficient background (GILZ-Lyn double knockout (DKO)) and compared them to WT and Lyn KO mice. The effects of GILZ deficiency on spleen weight, nephritis, serum autoantibodies and cytokines, and spleen cell expression of Type I interferon-induced genes (ISG) were examined.

Results: We observed heightened lupus-like autoimmunity in GILZ-Lyn DKO mice, compared to Lyn KO, that include increased spleen weight (p=0.041) and more severe glomerulonephritis, including worse glomerular segmental necrosis (p=0.0051) and crescent formation (p=0.0044) (Fig 1A-C). Despite this, serum levels of serum autoantibodies against ENAs (dsDNA, histone, Sm, Jo-1, U1RNP, Ro52, ribosomes, and Scl-70) and a panel of serum pro-inflammatory cytokines (BAFF, IL-6, IFNγ, IL-10 and TNFα) measured by Luminex assay were unaffected. In contrast, GILZ deficiency in Lyn deficient mice resulted in increased expression of ISG (ifi44, usp18, oas3, isg15, mx1, and irf7) and an overall ISG signature (p=0.0023) (Fig 1D).

Conclusion: In Lyn KO lupus-prone mice, GILZ deficiency significantly exacerbated disease expression, accompanied by activation of Type I IFN, despite serum autoantibody titres and pro-inflammatory cytokines being unaffected. This suggests an inhibitory effect of endogenous GILZ on Type I IFN pathways and consequent tissue injury in this model, downstream of autoantibodies. A GILZ-based treatment could be a potential therapeutic strategy in SLE.


Disclosure: C. Nataraja, None; E. Morand, None; J. Lee, None; T. Bennett, None; J. Flynn, None; J. Harris, None; S. Jones, None.

To cite this abstract in AMA style:

Nataraja C, Morand E, Lee J, Bennett T, Flynn J, Harris J, Jones S. Glucocorticoid-Induced Leucine Zipper (GILZ) Deficiency Worsens Autoimmunity in the Lyn-Deficient Murine Model of Lupus By Disinhibiting the Type I Interferon (IFN) Pathway [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/glucocorticoid-induced-leucine-zipper-gilz-deficiency-worsens-autoimmunity-in-the-lyn-deficient-murine-model-of-lupus-by-disinhibiting-the-type-i-interferon-ifn-pathway/. Accessed May 30, 2023.
  • Tweet
  • Email
  • Print

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/glucocorticoid-induced-leucine-zipper-gilz-deficiency-worsens-autoimmunity-in-the-lyn-deficient-murine-model-of-lupus-by-disinhibiting-the-type-i-interferon-ifn-pathway/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

© COPYRIGHT 2023 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences