Swiss HPB (Hepato-Pancreato-Biliary) Center, University Hospital Zürich, Switzerland.
Institute for Virology, Helmholtz-Zentrum München, Germany; Institute for Virology, Technische Universität München, Germany.
Cytokine Growth Factor Rev. 2014 Apr;25(2):125-37. doi: 10.1016/j.cytogfr.2014.01.003. Epub 2014 Jan 10.
The pathogenic mechanisms of autoimmune pancreatitis (AIP), an increasingly recognized, immune-mediated form of chronic pancreatitis, have so far remained elusive. Treatment options for AIP are currently limited and disease relapse is frequent. Still, AIP can be characterized by specific clinical and histologic features. It has turned out that as described in other autoimmune diseases the generation of tertiary lymphoid organs is also a hallmark of patients with AIP. We have recently demonstrated that pancreata derived from human AIP patients display overexpression of lymphotoxin (LT) α and β and LTβR-target genes expressed by immune cells but also by irradiation resistant cells of the pancreas (e.g. acinar cells). Expression of LT α and β on acinar cells in murine pancreata Tg(Ela1-Lta,b) mice led to chronic pancreatitis and sufficed to reproduce key features of human AIP including the development of autoimmunity and AIP associated secondary extra pancreatic pathologies. Here, we review how aberrant and ectopic expression of LT α and β can induce inflammation and autoimmune diseases in general and how this knowledge might specifically lead to an alternative treatment for patients suffering from autoimmune pancreatitis.
自身免疫性胰腺炎（AIP）的发病机制一直难以捉摸，AIP 是一种日益被认识的免疫介导性慢性胰腺炎。目前 AIP 的治疗选择有限，疾病复发频繁。尽管如此，AIP 可以通过特定的临床和组织学特征来描述。事实证明，正如在其他自身免疫性疾病中所描述的那样，三级淋巴器官的产生也是 AIP 患者的一个标志。我们最近表明，源自人类 AIP 患者的胰腺表现出淋巴毒素 (LT)α 和β以及 LTβR 靶向基因的过度表达，这些基因由免疫细胞表达，但也由胰腺（例如腺泡细胞）中辐射抗性细胞表达。在小鼠胰腺 Tg(Ela1-Lta,b)小鼠的腺泡细胞上表达 LTα 和β导致慢性胰腺炎，并足以复制人类 AIP 的关键特征，包括自身免疫和与 AIP 相关的继发性胰腺外病理的发展。在这里，我们回顾了 LTα 和β 的异常和异位表达如何一般诱导炎症和自身免疫性疾病，以及这些知识如何具体导致患有自身免疫性胰腺炎的患者的替代治疗。
