Emerging biochemical, microbial and immunological evidence in the search for why HLA-B∗27 confers risk for spondyloarthritis,Cell Chemical Biology

当前位置： X-MOL 学术 › Cell Chem. Bio. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Emerging biochemical, microbial and immunological evidence in the search for why HLA-B∗27 confers risk for spondyloarthritis
Cell Chemical Biology ( IF 6.6 ) Pub Date : 2024-08-20 , DOI: 10.1016/j.chembiol.2024.07.012
Eric M Brown ₁ , Phuong N U Nguyen ₂ , Ramnik J Xavier ₃

Affiliation

The strong association of the human leukocyte antigen B27 alleles () with spondyloarthritis and related rheumatic conditions has long fascinated researchers, yet the precise mechanisms underlying its pathogenicity remain elusive. Here, we review how interplay between the microbiome, the immune system, and the enigmatic HLA-B27 could trigger spondyloarthritis, with a focus on whether HLA-B27 presents an arthritogenic peptide. We propose mechanisms by which the unique biochemical characteristics of the HLA-B27 protein structure, particularly its peptide binding groove, could dictate its propensity to induce pathological T cell responses. We further provide new insights into how TRBV9 CD8 T cells are implicated in the disease process, as well as how the immunometabolism of T cells modulates tissue-specific inflammatory responses in spondyloarthritis. Finally, we present testable models and suggest approaches to this problem in future studies given recent advances in computational biology, chemical biology, structural biology, and small-molecule therapeutics.

中文翻译：

寻找 HLA-B*27 为何会带来脊柱关节炎风险的新生化、微生物和免疫学证据

人类白细胞抗原 B27 等位基因 () 与脊柱关节炎和相关风湿性疾病的密切相关性长期以来一直令研究人员着迷，但其致病性的确切机制仍然难以捉摸。在这里，我们回顾了微生物组、免疫系统和神秘的 HLA-B27 之间的相互作用如何引发脊柱关节炎，重点关注 HLA-B27 是否呈现致关节炎肽。我们提出了 HLA-B27 蛋白质结构的独特生化特征（特别是其肽结合沟）可能决定其诱导病理性 T 细胞反应的倾向的机制。我们进一步提供了关于 TRBV9 CD8 T 细胞如何参与疾病过程，以及 T 细胞的免疫代谢如何调节脊柱关节炎中组织特异性炎症反应的新见解。最后，鉴于计算生物学、化学生物学、结构生物学和小分子治疗学的最新进展，我们提出了可测试的模型，并建议在未来的研究中解决这个问题的方法。

更新日期：2024-08-20

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南