Autoimmune Pancreatitis Mouse Model

Ken Kamata1, Tomohiro Watanabe2, Kosuke Minaga1, Warren Strober2, Masatoshi Kudo1

1 Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka‐Sayama, Osaka, 2 Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda
Publication Name:  Current Protocols in Immunology
Unit Number:  Unit 15.31
DOI:  10.1002/cpim.41
Online Posting Date:  February, 2018
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Autoimmune pancreatitis (AIP) is a chronic fibro‐inflammatory disorder of the pancreas. However, extensive clinico‐pathological analyses have revealed that AIP is, in reality, a pancreatic manifestation of a newly described systemic disease known as IgG4‐related disease (IgG4‐RD). IgG4‐RD is characterized by enhanced local and systemic IgG4 antibody (Ab) responses as well as inflammation involving multiple organs, including the pancreas, bile ducts, and salivary glands. Although mice lack the IgG4 Ab subtype, autoimmune‐prone MRL/Mp mice treated with repeated injection with polyinosinic‐polycytidylic acid (poly (I:C)) provide an experimental model of AIP. These mice exhibit massive destruction of pancreatic architecture associated with pancreatic immune cell infiltration and fibrosis. Moreover, this experimental AIP may be accompanied by involvement of multiple organs as well as elevation of serum levels of autoAbs, resembling humans with IgG4‐RD. Thus, elucidation of the molecular mechanisms accounting for the development of experimental AIP can potentially provide new insights into the immuno‐pathogenesis of human IgG4‐related AIP. © 2018 by John Wiley & Sons, Inc.

Keywords: autoimmune pancreatitis; IgG4‐related disease; plasmacytoid dendritic cells

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Table of Contents

  • Introduction
  • Basic Protocol 1: Induction of Autoimmune Pancreatitis in MRL/Mp Mice
  • Support Protocol 1: Isolation of Pancreatic Mononuclear Cells
  • Commentary
  • Literature Cited
  • Figures
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Basic Protocol 1: Induction of Autoimmune Pancreatitis in MRL/Mp Mice

  • Endotoxin‐free physiological water (InvivoGen)
  • Poly (I:C), high molecular weight (InvivoGen)
  • 6‐ to 8‐week‐old female MRL/Mp Mice (Japan SLC or Charles River Laboratory)
  • 10% formalin (Wako Laboratory Chemicals)
  • PBS
  • Hematoxylin and eosin (H&E)
  • Sirius Red staining kit (Polysciences)
  • Alpha smooth muscle actin Ab (Abcam)
  • 65°to 70°C heating block or bath
  • 27‐ to 29‐G needles
  • 1‐ml syringes
  • Surgical instruments

Support Protocol 1: Isolation of Pancreatic Mononuclear Cells

  • Collagenase (Wako Laboratory Chemicals)
  • PBS without CaCl 2 or MgCl 2
  • DNase I (Roche)
  • RPMI1640
  • Heat‐inactivated FBS
  • Mouse pancreas
  • HBSS without CaCl 2 or MgCl 2
  • Percoll (GE‐Healthcare)
  • FITC‐conjugated B220 Ab (eBioscience)
  • PE‐conjugated PDCA‐1 Ab (eBioscience)
  • Petri dishes
  • 15‐ and 50‐ml centrifuge tubes (Falcon)
  • Refrigerated centrifuge
  • 37°C shaker
  • 70‐μm cell strainer (BD Falcon)
  • Centrifuge, room temperature
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Literature Cited

Literature Cited
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