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Mechanistic Insights into Autoimmune Pancreatitis and IgG4-Related Disease
Tomohiro Watanabe1, Kosuke Minaga2, Ken Kamata2
1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan; Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Autoimmune pancreatitis (AIP) is a pancreatic manifestation of a recently defined disease form known as IgG4-related disease (AIP/IgG4-RD). AIP/IgG4-RD is characterized by elevated systemic IgG4 antibody concentrations and lesional tissues infiltrated by IgG4-expressing plasmacytes. In addition, recent studies have revealed that, in common with other autoimmune diseases, such as systemic lupus erythematosus (SLE) and psoriasis, AIP/IgG4-RD is associated with increased type I IFN (IFN-I) production by plasmacytoid dendritic cells (pDCs). However, unlike SLE, AIP/IgG4-RD is characterized by elevated IFN-I-dependent IL-33 production, the latter emerging as an important contributor to inflammation and fibrotic responses characterizing this disease. On this basis, we propose that blockade of the IFN-I/IL-33 axis might constitute a successful approach to treating this unique type of autoimmunity.
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