Involvement of Inducible Costimulator- and Interleukin 10-Positive Regulatory T Cells in the Development of IgG4-Related Autoimmune Pancreatitis : Pancreas

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Involvement of Inducible Costimulator- and Interleukin 10-Positive Regulatory T Cells in the Development of IgG4-Related Autoimmune Pancreatitis

Kusuda, Takeo MD*; Uchida, Kazushige MD, PhD*; Miyoshi, Hideaki MD, PhD*; Koyabu, Masanori MD, PhD*; Satoi, Sohei MD, PhD†; Takaoka, Makoto MD, PhD*; Shikata, Nobuaki MD, PhD‡; Uemura, Yoshiko MD, PhD‡; Okazaki, Kazuichi MD, PhD*

Author Information

From the *Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, and Departments of †Surgery and ‡Pathology, Kansai Medical University, Osaka, Japan.

Received for publication September 21, 2010; accepted April 14, 2011.

Reprints: Kazuichi Okazaki, MD, PhD, The Third Department of Internal Medicine, Kansai Medical University, 10-15 Fumizonocho, Moriguchi, Osaka 570-8506, Japan (e-mail: [email protected]).

This study was partially supported by (1) Grant-in-Aid for Scientific Research (C) of the Ministry of Culture and Science of Japan (20590810, 23591017-0001), (2) Intractable Diseases, the Health and Labor Sciences Research Grants (KO) from the Minister of Labor and Welfare of Japan, and (3) grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, from CREST Japan Science and Technology Agency.

Pancreas 40(7):p 1120-1130, October 2011. | DOI: 10.1097/MPA.0b013e31821fc796

Abstract

Objectives: 

Immunoglobulin G4 (IgG4)-related autoimmune pancreatitis (AIP) is a new clinical entity of pancreatic disorder. There are immunologic and histological abnormalities, including increased serum IgG4 levels and the infiltration of IgG4-positive plasmacytes. However, the role of IgG4 is unclear. Recently, regulatory T cells (Tregs) were reported to contribute to the development of various autoimmune diseases as well as in B-cell shifting to IgG4-producing plasmacytes. We studied Tregs in the pancreas and peripheral blood.

Methods: 

We recruited 44 patients with IgG4-related AIP. For comparison, we recruited 37 patients with other pancreatic diseases and 27 healthy subjects as controls. We studied infiltrating cells in the pancreas by immunohistochemistry and analyzed inducible costimulator-positive Tregs and interleukin 10-positive Tregs in the peripheral blood by flow cytometry.

Results: 

The ratio of Foxp3-positive cells to infiltrated mononuclear cells (Foxp3/Mono) in AIP patients was significantly higher than in patients with alcoholic chronic pancreatitis. In AIP, Foxp3/Mono and IgG4/Mono were positively correlated. Inducible costimulator-positive Tregs were significantly higher in AIP patients than in the patients with other pancreatic diseases and the healthy control group. Interleukin 10-positive Tregs were significantly higher in AIP patients than in the healthy control group.

Conclusions: 

Increased quantities of inducible costimulator-positive Tregs may influence IgG4 production in IgG4-related AIP.

© 2011 Lippincott Williams & Wilkins, Inc.

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