Department   School of Medicine, School of Medicine
   Position   Professor and Division head
Article types Original article
Language English
Peer review Peer reviewed
Title A mouse model of autoimmune pancreatitis with salivary gland involvement triggered by innate immunity via persistent exposure to avirulent bacteria.
Journal Formal name:Laboratory investigation; a journal of technical methods and pathology
Abbreviation:Lab Invest
ISSN code:00236837/15300307
Volume, Issue, Page 90(12),pp.1757-1769
Author and coauthor HARUTA Ikuko†* ,YANAGISAWA Naoko, KAWAMURA Shunji, FURUKAWA Toru, SHIMIZU Kyoko, KATO Hidehito, KOBAYASHI Makio, SHIRATORI Keiko, YAGI Junji
Authorship 2nd author
Publication date 2010/12
Summary The pathogenesis of autoimmune pancreatitis (AIP) remains unknown. Here, we investigated the possible involvement of chronic, persistent exposure to avirulent bacteria in the pathogenesis of AIP. C57BL/6 mice were inoculated with heat-killed Escherichia coli weekly for 8 weeks. At 1 week and up to 12 months after the final inoculation, the mice were killed to obtain samples. At 1 week after the final E. coli inoculation, marked cellular infiltration with fibrosis was observed in the exocrine pancreas. Cellular infiltration in the exocrine pancreas was still observed up to 12 months after the completion of E. coli inoculation. At 10 months after the final inoculation, duct-centric fibrosis became obvious. Inflammation around the ducts in the salivary glands was also observed. Furthermore, sera from heat-killed E. coli-inoculated mice possessed anti-carbonic anhydrase, anti-lactoferrin, and antinuclear antibodies. Exposure to E. coli-triggered AIP-like pancreatitis in C57BL/6 mice. We propose a hypothetical mechanism for AIP pathogenesis. During the initiation phase, silently infiltrating pathogen-associated molecular patterns (PAMP) and/or antigen(s) such as avirulent bacteria might trigger and upregulate the innate immune system. Subsequently, the persistence of such PAMP attacks or stimulation by molecular mimicry upregulates the host immune response to the target antigen. These slowly progressive steps may lead to the establishment of AIP and associated extrapancreatic lesions. Our model might be useful for clarifying the pathogenesis of AIP.