Immune Netw.  2016 Dec;16(6):366-372. 10.4110/in.2016.16.6.366.

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

• Cho WS
• Jang E
• Kim HY
• Youn J

• KMID: 2362801
• DOI: http://doi.org/10.4110/in.2016.16.6.366

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.

Keyword

IL-17; Synovial cells; Arthritis; Immune complex

MeSH Terms

Animals
Antigen-Antibody Complex
Arthritis*
Autoantibodies
Interleukin-17
Interleukin-23
Interleukins*
Joints
Mice
Antigen-Antibody Complex
Autoantibodies
Interleukin-17
Interleukin-23
Interleukins

Figure

• 

  Figure 1 IL-17 is required for development of K/BxN serum-induced arthritis. IL-17−/− mice and their WT littermates were injected with K/BxN serum, disease was assessed for 12 days, and then mice were sacrificed for ex vivo assays. (A) Ankle thickness of hind-paws and arthritis index (n=15 per group). (B) Histopathologic examination of hind-paw sections. Original magnification, 100×. (C) Immunohistochemical staining of hind-paw sections with anti-IL-17 Ab. Original magnification, 200×. (D) Synovial tissues were assayed by RT-PCR. The arrow indicates IL-23. Data shown are pooled (A) or representative (B-D) results of three independent experiments. Graphs display means±SEMs. *p<0.05, **p<0.01, and ***p< 0.001 by Student's t-test. NT, no treatment; ST, serum transfer.

• 

  Figure 2 Phenotypes of IL-17-producing synovial cells. IL-17−/− mice and their WT littermates were administered K/BxN serum. Synovial cells were extracted from mice post-mortem (day 12 post-serum transfer) and analyzed by FACS. (A) FACS profiles of cells from WT mice, gated on live lymphocytes (R1) or FSCintSSCint cells (R2). (B) The FSCintSSCint cells were divided into three fractions, ScahiThy1hi (R3), Sca1intThy1hi (R4), and remaining (R5) cells, and the percentage of IL-17+ cells within each fraction is shown. (C) FACS profiles displaying Sca1 and Thy1 expression levels of R2-gated cells (the upper panel), and the percentage of IL-17+ cells within the R6 gate of upper graphs (the lower panel). Data are representative of three independent experiments. NT, no treatment; ST, serum transfer.

• 

  Figure 3 IL-23 and immune complexes promote IL-17 expression by Sca1intThy1hi synovial cells. Synovial cells extracted from normal mice were stimulated with 10 ng/ml IL-23 (A) or immune complexes (IC) (B) for 48 h, followed by RT-PCR and FACS analyses. FACS profiles gated on FSCintSSCint (upper panels) and R1 (lower panels) are shown. Data are representative of three independent experiments.

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