CIA mice

All animal experiments were approved by the Institutional Animal Care and Use Committee of the Jikei University, Tokyo, Japan. Five-week-old DBA/1 J mice (n = 69) were purchased from Sankyo Labo Service (Tokyo, Japan) and immunized intradermally at the dorsal root of the tail with bovine type II collagen (200 μg/mouse; Collagen Research Center, Tokyo, Japan) emulsified in Freund’s complete adjuvant (Becton Dickinson and Company, NJ, USA) (Day 0). On Day 21, a booster injection of bovine type II collagen emulsified in Freund’s incomplete adjuvant (Becton Dickinson and Company) was administered in the same manner. The severity of arthritis was evaluated by a clinical rheumatologist (study co-author KO), who was blinded to the study groups, and expressed as the sum of the scores for all four limbs as assessed on the following scale: 0, normal; 1, swelling of digits alone or mild swelling of wrist and ankle joints; 2, clear swelling of wrist and ankle joints; and 3, severe swelling of wrist and ankle joints.