ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Interleukin-24 involvement in the intestinal response to curdlan in SKG mice (#156)

Amy J Cameron 1 , Rabina Giri 2 , Jakob Begun 2 , Anne-Sophie Bergot 1 , Ranjeny Thomas 1
  1. The University of Queensland Diamantina Institute, Brisbane, QLD, Australia
  2. Mater Research Institute-UQ, Translational Research Institute, Brisbane, Australia

Spondyloarthropathy (SpA) encompasses a group of chronic auto-inflammatory diseases with characteristic symptoms affecting the joints and extra-articular sites such as the gut (1). In other models, interleukin-24 (IL-24) has been shown to promote ER stress-mediated apoptosis in damaged cancerous cells without affecting normal cells (2). In SpA, IL-24 was elevated in the synovial fluid of patients suggesting a role in SpA pathogenesis, however its direct actions are unknown (3). To explore the role of IL-24 in SpA, we used ZAP-70W163C BALB/c (SKG) mice that develop chronic joint inflammation and inflammatory bowel disease (IBD)-like ileitis in response to i.p. curdlan. Prior to curdlan, endoplasmic reticulum (ER) stress and interleukin-23 (IL-23) are increased in the SKG ileum, and there is fecal dysbiosis (4). Within 1 week post-curdlan, SKG ileum displays reduced mucus secretion, goblet cell loss and gut microbial permeability (5). Using RT-qPCR gene expression analysis, Il24 mRNA expression was increased in the ileum of SKG mice compared to BALB/c controls before or after curdlan. Il24 positively correlated with mRNA expression of the ER stress markers Grp78 and sXBP1 in the ileum of SKG mice. By immunofluorescent staining, IL-24 co-localized to the goblet cells of the ileum in naive SKG mice. Goblet cells were lost and IL-24 staining concomitantly decreased 2 weeks post curdlan. In the human goblet cell line, LS174T, cultured with the ER stress inducer tunicamycin, Il24 mRNA was transiently expressed after 2hr, preceding the expression of Grp78 and sXBP1. Together, our data demonstrate that IL-24 is found in goblet cells and is over-expressed in SKG ileum. The correlation of IL-24 and ER stress markers in the gut and the temporal expression in stressed human goblet cells suggests that in SpA, goblet cells become susceptible to IL-24-mediated apoptosis.

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