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

  • Eur J Pharmacol. 2026 May 10:1023:178881. doi: 10.1016/j.ejphar.2026.178881.
Dingding Zhang  1 ,  Lisheng Wu  1 ,  Feilong Chen  1 ,  Xiaoyun Chen  2 ,  Songyuan Zheng  2 ,  Juan Li  3 ,  Shixian Chen  4
Affiliations
  • 1. Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, 510315, China.
  • 2. Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • 3. Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, 510315, China; Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
  • 4. Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: [email protected].
PMID: 42000020 DOI: 10.1016/j.ejphar.2026.178881
Abstract

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.

Keywords
Autoantigen; Collagen-induced arthritis; Dendritic cell; Rheumatoid arthritis; Sinomenine; T cell.
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