Background/Purpose: Interferon regulatory factor 5 (IRF5) is a transcription factor that mediates signals activated by engagement of Toll-like receptors (TLRs). IRF5 polymorphisms are associated with the risk of systemic autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Although it has been shown that IRF5 has crucial roles in the development of lupus in murine models, its role in arthritis has yet to be fully investigated. Therefore, the role of IRF5 in the development of murine collagen-induced arthritis (CIA) was examined.

Methods: CIA was induced in IRF5-deficient, IRF5-heterozygous, and wild-type DBA/1 mice by injecting type II collagen (CII) emulsified with CFA followed by CII with IFA 21 days later. The incidence and severity of arthritis were then evaluated, and cytokine production by spleen cells in response to CII and serum anti-CII antibody levels were determined. Wild-type mice were treated with IRF5-specific siRNA during the progression phase of CIA. For non-specific suppression, siRNA was mixed with atelocollagen and injected intravenously. For antigen-presenting cell (APC)-specific suppression, siRNA was mixed with schizophyllan, a beta-glucan that binds to dectin-1, and injected intraperitoneally.

Results: IRF5-deficient mice developed a similar degree of arthritis as wild-type mice. However, IRF5-heterozygous mice showed reduced incidence and severity of arthritis compared with wild-type or IRF5-deficient mice. The final incidence was 79%, 56%, and 75%, and the mean arthritis index was 4.8, 1.8, and 4.2, in IRF5+/+, IRF5+/-, and IRF5-/- mice, respectively. These data suggest that IRF5 has the dual effects of suppression and promotion in the development of CIA. IRF5-deficient mice showed decreased levels of anti-CII antibody, but spleen cells from IRF5-deficient mice produced higher amounts of IL-17 in response to CII. Administration of siRNA by a non-specific delivery system during the course of CIA attenuated the arthritis in wild-type mice. In contrast, treatment with siRNA by an APC-specific delivery system significantly exacerbated the CIA.

Conclusion: IRF5 has roles in anti-CII antibody production and Th17 induction, and it shows both pro- and anti-inflammatory effects in the development of CIA. IRF5 in APCs has a regulatory role in the development of CIA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pro-inflammatory-and-anti-inflammatory-roles-of-interferon-regulatory-factor-5-in-the-development-of-collagen-induced-arthritis/