Glucosamine induces Th17 cell differentiation by inhibiting CD122 expression which results in the aggravation of collagen-induced arthritis

초록

D-glucosamine (GlcN) is known to have a therapeutic role in osteoarthritis. However, effect of GlcN on rheumatoid arthritis and molecular mechanisms how GlcN influences on immune cells are not fully understood. First, we investigated to understand the mechanism how GlcN influences on the T cell activation in vitro. We obtained the following results; 1) GlcN inhibited the T-cell proliferation and division. 2) Interleukin-2 (IL-2) production was significantly increased in GlcN-treated T cell culture medium. 3) IL-2 receptor beta chain (CD122) was significantly decreased by GlcN. 4) GlcN markedly reduced the IFN-γ and IL-17A expression. According to the inhibitory role of GlcN on T cells, we investigated whether GlcN has a therapeutic efficacy in collagen-induced arthritis. Surprisingly, in contrast to the results in vitro, mice received GlcN showed early onset and increased severity. Since IL-17 plays as a pathogenic cytokine in rheumatoid arthritis, we differentiated CD4+ T cells into Th17 cells. GlcN significantly increased Th17 differentiation and inhibited CD122 expression. Thus, GlcN induces Th17 cell differentiation by inhibiting IL-2 signaling, which may result in the aggravation of collagen-induced arthritis.