Background/Purpose: Hydrodynamic injection of IL-23 minicircles into adult B10.RIII mice induces an inflammatory disease with phenotypic features of human spondyloarthritis. Tissue-resident CD4-CD8- double negative (DN) T cells secreting IL-17A in response to stimulation with IL-23 are thought to be critical in this model. To further dissect disease pathogenesis, IL-23 minicircle injection into genetically modified mice would be informative. C57BL/6, the background strain for most genetically engineered mice, has been shown to be less permissive than B10.RIII in several autoimmune or inflammatory disease models. Here, we tested the susceptibility of C57BL/6 mice to IL-23 minicircle-induced spondyloarthritis and compared number and function of DN T cells between C57BL/6 and B10.RIII mice.

Methods: Adult C57BL/6 and B10.RIII mice were injected with IL-23 minicircles and monitored clinically for disease development. IL-23 induction was measured by quantitative PCR (liver tissue) and ELISA (serum). Single cells suspensions were prepared from blood, liver, spleen, skin and the Achilles tendon enthesis. Cells were analyzed by multicolor flow cytometry. IL-17A production was measured by intracellular staining after stimulation with IL-23/IL-1β or PMA/Ionomycin in the presence of Golgi-Stop for 4 hours.

Results: In contrast to B10.RIII mice, C57BL/6 mice were resistant to induction of IL-23 minicircle-induced spondyloarthritis. While IL-23 expression did not differ between the two strains, C57BL/6 mice failed to develop paw swelling or psoriasis-like skin changes over the observation period of up to 4 weeks. Frequency and number of DN αβ and γδ T cells were not different in the five tissues analyzed. However, upon in vitro stimulation, we observed a statistically significantly higher frequency of IL-17A positive DN αβ T cells in susceptible B10.RIII mice compared with resistant C57BL/6 animals.

Conclusion: C57BL/6 mice in our animal facility are resistant to IL-23 minicircle-induced spondyloarthritis, which limits the utility of this model for mechanistic studies. IL-17A secretion by DN αβ T cell but not γδ T cells correlated with strain-dependent disease susceptibility.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/strain-dependent-il-17a-secretion-by-cd4-cd8-dn-%ce%b1%ce%b2-t-cells-correlates-with-disease-susceptibility-in-murine-spondyloarthritis/