Sinomenine modulates autoantigen-specific immune responses by inhibiting dendritic cell activation in experimental arthritis.

BACKGROUND

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic joint inflammation. Although sinomenine (SIN) is clinically effective against RA, its potential to modulate autoantigen-specific immune responses and the underlying mechanisms remain incompletely understood.

METHODS

Spleen and lymph node cells from collagen-induced arthritis (CIA) mice were cultured to investigate the effects of SIN on type II collagen (CII)-induced T cell activation both in vivo and in vitro. Antibody levels and T cell subsets proportions were also assessed. Bone marrow-derived dendritic cells (BMDCs) were generated and activated with TNF-α, and the effects of SIN on dendritic cell (DC) maturation and activation were examined.

RESULTS

SIN markedly suppressed CII-induced T cell activation in vitro, but did not affect T cell activation induced by TCR mimetics anti-CD3 and anti-CD28 antibodies. SIN also lowered CD80 and CD86 expression on TNF-α-activated BMDCs, reduced IL-6 and IL-12 secretion, and downregulated Il-6, Il-12, and Tnf-α mRNA expression. In vivo SIN intervention prior to arthritis onset suppressed CII-induced T cell activation in lymph node cells upon ex vivo stimulation, decreased serum anti-CII antibodies, lowered Th1 and Th17 cell proportions, and increased the frequency of Treg cells. Moreover, administration of SIN reduced MHC-II expression on cDC1 in draining lymph nodes after CII/CFA immunization.

CONCLUSION

SIN inhibits the activation of DCs, leading to suppressed T cell activation induced by autoantigen CII. SIN also shifts the T cell subset balance toward immunotolerance. Together, these effects alleviate the inflammatory response in CIA mice.