Mechanistic Insights into Autoimmune Pancreatitis and IgG4-Related Disease

Trends Immunol. 2018 Nov;39(11):874-889. doi: 10.1016/j.it.2018.09.005. Epub 2018 Oct 25.

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.

Keywords: IFN-I; IL-33; IgG4-related disease; autoimmune pancreatitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Humans
  • Immunoglobulin G4-Related Disease / immunology*
  • Interferon Type I / metabolism
  • Interleukin-33 / metabolism
  • Mice
  • Pancreatitis / immunology*

Substances

  • Interferon Type I
  • Interleukin-33