Suppression of T cell responses by chondromodulin I, a cartilage-derived angiogenesis inhibitory factor: Therapeutic potential in rheumatoid arthritis
✍ Scribed by Keigo Setoguchi; Yoshikata Misaki; Kimito Kawahata; Kota Shimada; Takuo Juji; Sakae Tanaka; Hiromi Oda; Chisa Shukunami; Yuriko Nishizaki; Yuji Hiraki; Kazuhiko Yamamoto
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 393 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Objective
Chondromodulin I (ChM‐I), a cartilage matrix protein, promotes the growth and proteoglycan synthesis of chondrocytes. However, it also inhibits angiogenesis. Since ChM‐I is expressed not only in cartilage, but also in the thymus, we investigated the modulation of T cell function by ChM‐I to assess its therapeutic potential in rheumatoid arthritis (RA).
Methods
The localization of ChM‐I expression in mouse thymus tissue was examined by in situ hybridization. The proliferative response of peripheral blood T cells and synovial cells obtained from patients with RA was evaluated by ^3^H‐thymidine incorporation assay. The effects of ChM‐I were examined using recombinant human ChM‐I (rHuChM‐I). Modulation of the antigen‐specific immune response was evaluated by the recall response of splenic T cells and the delayed‐type hypersensitivity response induced in the ear of mice primed with ovalbumin (OVA). Antigen‐induced arthritis (AIA) was induced in mice by injecting methylated bovine serum albumin into the ankle joints 2 weeks after the priming.
Results
ChM‐I was expressed in the cortex of the thymus. Recombinant human ChM‐I suppressed the proliferative response of mouse splenic T cells and human peripheral blood T cells stimulated with anti‐CD3/CD28 antibodies, in a dose‐dependent manner. Production of interleukin‐2 was decreased in rHuChM‐I–treated mouse CD4 T cells. Ten micrograms of rHuChM‐I injected intraperitoneally into OVA‐primed mice suppressed the induction of the antigen‐specific immune response. Finally, rHuChM‐I suppressed the development of AIA, and also suppressed the proliferation of synovial cells prepared from the joints of patients with RA.
Conclusion
These results suggest that ChM‐I suppresses T cell responses and synovial cell proliferation, implying that this cartilage matrix protein has a therapeutic potential in RA.