University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Department of Immunology and Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Immunol Rev. 2024 Aug;325(1):90-106. doi: 10.1111/imr.13359. Epub 2024 Jun 12.
Rheumatoid arthritis (RA) is considered a multifactorial condition where interaction between the genetic and environmental factors lead to immune dysregulation causing autoreactivity. While among the various genetic factors, HLA-DR4 and DQ8, have been reported to be the strongest risk factors, the role of various environmental factors has been unclear. Though events initiating autoreactivity remain unknown, a mucosal origin of RA has gained attention based on the recent observations with the gut dysbiosis in patients. However, causality of gut dysbiosis has been difficult to prove in humans. Mouse models, especially mice expressing RA-susceptible and -resistant HLA class II genes have helped unravel the complex interactions between genetic factors and gut microbiome. This review describes the interactions between HLA genes and gut dysbiosis in sex-biased preclinical autoreactivity and discusses the potential use of endogenous commensals as indicators of treatment efficacy as well as therapeutic tool to suppress pro-inflammatory response in rheumatoid arthritis.
类风湿关节炎（RA）被认为是一种多因素疾病，其中遗传和环境因素的相互作用导致免疫失调，引起自身免疫反应。虽然在各种遗传因素中，HLA-DR4 和 DQ8 已被报道为最强的危险因素，但各种环境因素的作用尚不清楚。尽管自身反应性的起始事件仍不清楚，但基于最近观察到的患者肠道菌群失调，RA 的黏膜起源引起了关注。然而，肠道菌群失调的因果关系在人类中很难证明。小鼠模型，特别是表达 RA 易感和抗性 HLA Ⅱ类基因的小鼠，有助于揭示遗传因素和肠道微生物组之间的复杂相互作用。本文综述了 HLA 基因与肠道菌群失调在性别偏向性临床前自身反应性中的相互作用，并讨论了内源性共生菌作为治疗效果指标的潜在用途，以及作为抑制类风湿关节炎促炎反应的治疗工具。
