The role of lymphotoxin signaling in the development of autoimmune pancreatitis and associated secondary extra-pancreatic pathologies

作者：Seleznik Gitta Maria; Zoller Jessica; O'Connor Tracy; Graf Rolf; Heikenwalder Mathias^*

来源：Cytokine & Growth Factor Reviews, 2014, 25(2): 125-137.

DOI：10.1016/j.cytogfr.2014.01.003

• Lymphotoxin
• Pancreatitis
• Autoimmunity
• Tertiary lymphoid organ

The pathogenic mechanisms of autoimmune pancreatitis (AIP), an increasingly recognized, immunemediated 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) alpha and beta and LT beta R-target genes expressed by immune cells but also by irradiation resistant cells of the pancreas (e.g. acinar cells). Expression of LT alpha and beta 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 alpha and beta 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.

• 出版日期2014-4