European journal of pharmacology · 2026
Sinomenine modulates autoantigen-specific immune responses by inhibiting dendritic cell activation in experimental arthritis.
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Zhang Dingding, Wu Lisheng, Chen Feilong, Chen Xiaoyun, Zheng Songyuan, Li Juan, Chen Shixian
Аннотация
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.
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.