IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2+Vγ6+γδ T cells

Citations Over TimeTop 10% of 2015 papers

Abstract

Interleukin-17 (IL-17)-producing γδ T (γδ17) cells have been implicated in inflammatory diseases, but the underlying pathogenic mechanisms remain unclear. Here, we show that both CD4(+) and γδ17 cells are required for the development of autoimmune arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Specifically, activated CD4(+) T cells direct γδ T-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17 reporter mice reveal that the Vγ6(+) subset of CCR2(+) γδ T cells preferentially produces IL-17 in inflamed joints. Importantly, because IL-1Ra normally suppresses IL-1R expression on γδ T cells, IL-1Ra-deficient mice exhibit elevated IL-1R expression on Vγ6(+) cells, which play a critical role in inducing them to produce IL-17. Our findings demonstrate a pathogenic mechanism in which adaptive and innate immunity induce an autoimmune disease in a coordinated manner.

Related Papers

• → Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration*(2017)96 cited
• → Studying the Pharmacokinetics of Interleukin-1RA Mutants(2019)1 cited
• → Activity of an Interleukin 1 Receptor Antagonist in Rabbit Models of Uveitis(1992)58 cited
• → Role of Interleukin-1/Interleukin-1 Receptor Antagonist Family of Cytokines in Long-Term Continuous Glucose Monitoring In Vivo(2013)8 cited
• Correlation between osteoarthritis and interleukin-1 receptor antagonist(2007)