Floreani Annarosa, Leung Patrick S C, Gershwin M Eric
Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
Division of Rheumatology, Allergy, and Clinical Immunology, University of California Davis, Davis, CA, USA.
Clin Rev Allergy Immunol. 2016 Jun;50(3):287-300. doi: 10.1007/s12016-015-8493-8.
The three common themes that underlie the induction and perpetuation of autoimmunity are genetic predisposition, environmental factors, and immune regulation. Environmental factors have gained much attention for their role in triggering autoimmunity, with increasing evidence of their influence as demonstrated by epidemiological studies, laboratory research, and animal studies. Environmental factors known to trigger and perpetuate autoimmunity include infections, gut microbiota, as well as physical and environmental agents. To address these issues, we will review major potential mechanisms that underlie autoimmunity including molecular mimicry, epitope spreading, bystander activation, polyclonal activation of B and T cells, infections, and autoinflammatory activation of innate immunity. The association of the gut microbiota on autoimmunity will be particularly highlighted by their interaction with pharmaceutical agents that may lead to organ-specific autoimmunity. Nonetheless, and we will emphasize this point, the precise mechanism of environmental influence on disease pathogenesis remains elusive.
自身免疫性疾病的诱导和持续存在所基于的三个共同主题是遗传易感性、环境因素和免疫调节。环境因素因其在触发自身免疫性疾病中的作用而备受关注，流行病学研究、实验室研究和动物研究越来越多地证明了它们的影响。已知会触发并使自身免疫性疾病持续存在的环境因素包括感染、肠道微生物群以及物理和环境因素。为了解决这些问题，我们将回顾自身免疫性疾病潜在的主要机制，包括分子模拟、表位扩展、旁观者激活、B细胞和T细胞的多克隆激活、感染以及固有免疫的自身炎症激活。肠道微生物群与自身免疫性疾病的关联将因其与可能导致器官特异性自身免疫性疾病的药物的相互作用而得到特别强调。尽管如此，我们要强调这一点，环境对疾病发病机制影响的确切机制仍然难以捉摸。
