Strober Warren, Fuss Ivan J, Blumberg Richard S
Mucosal Immunity Section, Laboratory of Clinical Investigation, NIAID, NIH, Bethesda, Maryland 20892-1890, USA.
Annu Rev Immunol. 2002;20:495-549. doi: 10.1146/annurev.immunol.20.100301.064816. Epub 2001 Oct 4.
In recent years the status of the inflammatory bowel diseases (IBDs) as canonical autoimmune diseases has risen steadily with the recognition that these diseases are, at their crux, abnormalities in mucosal responses to normally harmless antigens in the mucosal microflora and therefore responses to antigens that by their proximity and persistence are equivalent to self-antigens. This new paradigm is in no small measure traceable to the advent of multiple models of mucosal inflammation whose very existence is indicative of the fact that many types of immune imbalance can lead to loss of tolerance for mucosal antigens and thus inflammation centered in the gastrointestinal tract. We analyze the immunology of the IBDs through the lens of the murine models, first by drawing attention to their common features and then by considering individual models at a level of detail necessary to reveal their individual capacities to provide insight into IBD pathogenesis. What emerges is that murine models of mucosal inflammation have given us a road map that allows us to begin to define the immunology of the IBDs in all its complexity and to find unexpected ways to treat these diseases.
近年来,随着人们认识到炎症性肠病(IBD)本质上是黏膜对黏膜微生物群中通常无害抗原的反应异常,因此是对因其接近性和持续性而等同于自身抗原的抗原的反应,IBD作为典型自身免疫性疾病的地位稳步上升。这种新范式在很大程度上可追溯到多种黏膜炎症模型的出现,这些模型的存在表明许多类型的免疫失衡会导致对黏膜抗原的耐受性丧失,从而引发以胃肠道为中心的炎症。我们通过小鼠模型来分析IBD的免疫学,首先关注它们的共同特征,然后在必要的细节层面考虑各个模型,以揭示它们为深入了解IBD发病机制提供见解的各自能力。结果表明,黏膜炎症的小鼠模型为我们提供了一个路线图,使我们能够开始全面定义IBD的免疫学,并找到治疗这些疾病的意想不到的方法。