Interleukin-1 receptor type 2 suppresses collagen-induced arthritis by inhibiting interleukin-1 signal on macrophages — ASN Events
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  2. Poster Session 2
  3. Interleukin-1 receptor type 2 suppresses collagen-induced arthritis by inhibiting interleukin-1 signal on macrophages

Interleukin-1 receptor type 2 suppresses collagen-induced arthritis by inhibiting interleukin-1 signal on macrophages (#331)

Kenji Shimizu 1 2 , Akiko Nakajima 3 , Katsuko Sudo 3 4 , Yang Liu 3 5 , Atsuhiko Mizoroki 3 , Reiko Horai 3 6 , Shigeru Kakuta 3 7 , Yoichiro Iwakura 1 3 8
  1. Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda City, Japan
  2. Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  3. Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  4. Animal Research Center, Tokyo Medical University, Tokyo, Japan
  5. Stem Cell Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  6. Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA
  7. Department of Biomedical Science, Graduate School of Agricultural and Life Science, The University of Tokyo, Tokyo, Japan
  8. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan

Background and aims

Interleukin-1 plays important roles in host defense against infection and inflammatory diseases. IL-1 receptor type 1 is the receptor for IL-1, and IL-1 receptor type 2 (IL-1R2) is suggested to be a decoy receptor, because it lacks signal transducing TIR domain in the cytoplasmic part. The roles of IL-1R2 in health and diseases, however, remain largely unknown. Rheumatoid arthritis (RA) is a typical autoimmune disease affecting approximately 1% of people worldwide independently of races. Because the concentration of IL-1R2 protein is increased in the synovial fluid and plasma in RA patients, the involvement of IL-1R2 in the pathogenesis is suggested. In this report, we demonstrated the roles of IL-1R2 in the development of arthritis.

Methods and results

We generated EGFP-knock-in Il1r2-/- mice and showed that Il1r2-/- mice were highly susceptible to collagen-induced arthritis, an animal model for rheumatoid arthritis. Il1r2 was highly expressed in neutrophils but only low in other cells including monocytes and macrophages. Antibody production and T cell responses against type II collagen were normal in Il1r2-/- mice. In spite of the high expression in neutrophils, no effects of Il1r2 deficiency were observed in neutrophils. On the other hand, we found that the production of inflammatory mediators in response to IL-1 was greatly enhanced in Il1r2-/- macrophages.

Conclusion

IL-1R2 is an important regulator of arthritis by acting specifically on macrophages as a decoy receptor for IL-1.