Chicken type II collagen induced immune balance of main subtype of helper T cells in mesenteric lymph node lymphocytes in rats with collagen-induced arthritis

Objective To investigate the effect of the oral administration of chicken type II collagen (CCII) on T cells from mesenteric lymph node (MLN) lymphocytes in rats with collagen-induced arthritis (CIA). Methods CIA was induced in male Sprague-Dawley rats immunized with CCII in Freund's complete adjuvant. CCII (10, 20, and 40 μg kg^-1 day^-1, i.g. × 7 days) was administered orally to rats from day 14 to 21 after immunization. Arthritis was evaluated by hind paw swelling and polyarthritis index, and MLNs and synovium were harvested for histological examination. Activity of interleukin-2 (IL-2) in MLN lymphocyte supernatant was measured by ConA-induced splenocyte proliferation in C57BL/6J mice, and IL-4, IL-17, and transforming growth factor beta (TGF-β) levels in MLN lymphocytes were measured by enzyme-linked immunosorbent assay (ELISA). The proportion of CD4⁺CD25⁺ Treg cells and Th17 cells was determined by double-color labeling for flow cytometry analysis. Results The administration of CCII (10, 20, 40 μg/kg, i.g. × 7 days) suppressed secondary inflammatory reactions and histological changes in CIA model. The activity of IL-2 and IL-17 produced by MLN lymphocytes from CIA rats was significantly inhibited by the administration of CCII (10, 20, and 40 lg kg^-1 day^-1). The levels of IL-4 and TGF-β were increased in CCII (10, 20, and 40 lg kg^-1 day^-1) groups. The flow cytometry analysis showed that CCII (10, 20, and 40 lg kg^-1 day^-1) significantly increased the proportion of Treg and decreased the proportion of Th17. Conclusion These results indicate that oral administration of CCII had therapeutic effects on CIA rats, which was related to decreased production of pro-inflammatory mediators (IL-2, IL-17) and increased production of antiinflammatory mediators (IL-4, TGF-β). This suggests that CCII plays an important role in regulating the immune balance of Th1/Th2 and Th17/Treg in rats with CIA.