カトウ　ヒデヒト   Katou Hidehito   加藤　秀人    所属   医学部 医学科    職種   非常勤講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	A mouse model of autoimmune pancreatitis with salivary gland involvement triggered by innate immunity via persistent exposure to avirulent bacteria.
掲載誌名	正式名：Laboratory investigation; a journal of technical methods and pathology 略　 称：Lab Invest ISSNコード：00236837/15300307
巻・号・頁	90(12),pp.1757-1769
著者・共著者	HARUTA Ikuko†* ,YANAGISAWA Naoko, KAWAMURA Shunji, FURUKAWA Toru, SHIMIZU Kyoko, KATO Hidehito, KOBAYASHI Makio, SHIRATORI Keiko, YAGI Junji
発行年月	2010/12
概要	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.