Details

Autor(en) / Beteiligte

• Zeng, Xiangchang
• Li, Chaopeng
• Liu, Yating
• Liu, Wenhui
• Hu, Yuwei
• Chen, Lulu
• Huang, Xinyi
• Li, Ying
• Hu, Kai
• Ouyang, Dongsheng
• Rao, Tai

Titel

HLA-B35:01-mediated activation of emodin-specific T cells contributes to Polygonum multiflorum thunb. -induced liver injury in mice

Ist Teil von

• Journal of ethnopharmacology, 2024-11, Vol.334, p.118523, Article 118523

Ort / Verlag

Elsevier B.V

Erscheinungsjahr

2024

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• HLA-B*35:01 has been identified as a risk allele for Polygonum multiflorum Thunb.-induced liver injury (PMLI). However, the immune mechanism underlying HLA-B*35:01-mediated PMLI remains unknown. To characterize the immune mechanism of HLA-B*35:01-mediated PMLI. Components of P. multiflorum (PM) bound to the HLA-B*35:01 molecule was screened by immunoaffinity chromatography. Both wild-type mice and HLA-B*35:01 transgenic (TG) mice were treated with emodin. The levels of transaminases, histological changes and T-cell response were assessed. Splenocytes from emodin-treated mice were isolated and cultured in vitro. Phenotypes and functions of T cells were characterized upon drug restimulation using flow cytometry or ELISA. Emodin-pulsed antigen-presenting cells (APCs) or glutaraldehyde-fixed APCs were co-cultured with splenocytes from emodin-treated transgenic mice to detect their effect on T-cell activation. Emodin, the main component of PM, could non-covalently bind to the HLA-B*35:01-peptide complexes. TG mice were more sensitive to emodin-induced immune hepatic injury, as manifested by elevated aminotransferase levels, infiltration of inflammatory cells, increased percentage of CD8+T cells and release of effector molecules in the liver. However, these effects were not observed in wild-type mice. An increase in percentage of T cells and the levels of interferon-γ, granzyme B, and perforin was detected in emodin-restimulated splenocytes from TG mice. Anti-HLA-I antibodies inhibited the secretion of these effector molecules induced by emodin. Mechanistically, emodin-pulsed APCs failed to stimulate T cells, while fixed APCs in the presence of emodin could elicit the secretion of T cell effector molecules. The HLA-B*35:01-mediated CD8+ T cell reaction to emodin through the P–I mechanism may contribute to P. multiflorum-induced liver injury. [Display omitted] •Emodin could bind to the HLA-B*35:01 molecule.•The HLA-B*35:01 transgenic mice are more susceptible to liver injury caused by emodin.•Activation of emodin-specific CD8+ T cells may be mediated by HLA-B*35:01.•HLA-B*35:01-mediated CD8+ T cell responses to emodin through the P–I mechanism.