Mannan activates a complement component, C5a, and promotes the production of inflammatory cytokines, such as TNF-α and IL-6, from macrophages and synovial fibroblasts, followed by differentiation and activation of CD4+Th17 cells in synovial tissue [1, 22], finally leading to early onset of RA in SKG mice. Here, TNF is linked to rheumatoid arthritis.