Interleukin 17-expressing Innate Synovial Cells Drive K/Bxn Serum-induced Arthritis

ABSTRACT

K/BxN serum can induce arthritis in normal mice because of abundant autoantibodies that trigger an innate inflammatory response in joints. To determine whether IL-17 is involved in the pathogenesis of serum-induced arthritis, we injected wild-type and IL-17(−/−) mice with K/BxN serum and evaluated them for signs of arthritis. Unlike wild-type mice, IL-17(−/−) mice did not show any signs of arthritis. IL-17 was produced predominantly by CD3⁻ CD4⁻γδTCR⁻ NK1.1⁻ Sca1(int) Thy1(hi) cells residing in the inflamed synovial tissue. When synovial cells extracted from normal joints were stimulated with IL-23 or autoantibody-containing immune complexes, a substantial fraction of Sca1(int) Thy1(hi) cells produced IL-17. Thus, we have identified a novel population of IL-17-producing innate synovial cells that play a crucial role in the development of K/BxN serum-induced arthritis.