Liberal Rodrigo, Grant Charlotte R, Longhi Maria Serena, Mieli-Vergani Giorgina, Vergani Diego
Institute of Liver Studies and Paediatric Liver, GI & Nutrition Centre, King's College London School of Medicine at King's College Hospital, London, UK.
IUBMB Life. 2015 Feb;67(2):88-97. doi: 10.1002/iub.1349. Epub 2015 Apr 8.
There are three classic liver diseases with probable autoimmune etiology: primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. The occurrence of these autoimmune conditions is determined by the breakdown of immune-regulatory mechanisms that in health are responsible for maintaining immunological tolerance against self-antigens. Among the multiple T cell subsets with suppressive function, the regulatory T cells (Tregs), defined by the expression of CD4, the IL-2 receptor α chain (CD25), and the transcription factor FOXP3, have emerged as having a central role in maintaining immune-tolerance to autoantigens. Tregs are equipped with an array of mechanisms of suppression, including the modulation of antigen presenting cell maturation and function, the killing of target cells, the disruption of metabolic pathways, and the production of anti-inflammatory cytokines. In all the three autoimmune liver diseases mentioned above, there is evidence pointing for either a reduced frequency and/or function of Tregs. Here, we review the definition, phenotypic characteristics, and mechanisms of suppression employed by Tregs and then we discuss the evidence available pointing to their impairment in patients with autoimmune liver disease.
原发性胆汁性肝硬化、原发性硬化性胆管炎和自身免疫性肝炎。这些自身免疫性疾病的发生是由免疫调节机制的破坏所决定的，在健康状态下，这些机制负责维持对自身抗原的免疫耐受。在具有抑制功能的多个T细胞亚群中，由CD4、白细胞介素-2受体α链（CD25）和转录因子FOXP3的表达所定义的调节性T细胞（Tregs），已成为在维持对自身抗原的免疫耐受中起核心作用的细胞。Tregs具备一系列抑制机制，包括调节抗原呈递细胞的成熟和功能、杀伤靶细胞、破坏代谢途径以及产生抗炎细胞因子。在上述所有三种自身免疫性肝病中，都有证据表明Tregs的频率和/或功能降低。在此，我们回顾Tregs的定义、表型特征和抑制机制，然后讨论现有证据表明其在自身免疫性肝病患者中的功能受损情况。
