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01-08-2020 | Autoimmune Pancreatitis | Original Article—Liver, Pancreas, and Biliary Tract

Interleukin-35 promotes the differentiation of regulatory T cells and suppresses Th2 response in IgG4-related type 1 autoimmune pancreatitis

Authors: Takashi Ito, Toshihiro Tanaka, Koh Nakamaru, Takashi Tomiyama, Takashi Yamaguchi, Yugo Ando, Tsukasa Ikeura, Toshiro Fukui, Kazushige Uchida, Akiyoshi Nishio, Kazuichi Okazaki

Published in: Journal of Gastroenterology | Issue 8/2020

Abstract

Background

IgG4-related disease (IgG4-RD) is a systemic inflammatory disease, which includes type 1 autoimmune pancreatitis (AIP). Interleukin-35 (IL-35) exhibits immunosuppressive effects in several autoimmune diseases. However, the expression of IL-35 had not been reported so far in type 1 AIP. We evaluated the association between IL-35 and several cytokines, which mediate the function of Tregs in type 1 AIP.

Methods

Plasma was collected from patients with type 1 AIP, alcoholic chronic pancreatitis (ACP), and healthy controls (HC) and assayed for cytokine expression. Total mRNA separated from peripheral blood was isolated from naïve Tregs (nTregs) and effector Tregs (eTregs). EBI3 and IL-12p35 gene expressions were tested in these cells by quantitative PCR. In addition, expression of IL-35 subunits in the pancreatic tissues of patients with type 1 AIP and ACP was analyzed by immunohistochemistry.

Results

IL-35 was significantly elevated in type 1 AIP (n = 32) plasma compared with ACP (n = 16) and HC (n = 22), but IL-27 was not. We also detected many cells expressing both EBI3 and IL-12p35 in type 1 AIP tissues. Moreover, in peripheral blood lymphocyte, the percentage of nTregs and eTregs of CD4⁺ T cells in patients with type 1 AIP (n = 14) compared with HC (n = 15) was significantly decreased and increased, respectively. There were no significant differences of gene expression in patients with type 1 AIP and HC.

Conclusions

This study identified elevated expression of plasma IL-35 and tissue IL-35 subunits in patients with type 1 AIP. This might lead to inflammation suppression via activated eTregs. IL-35 might be associated with this anti-inflammatory role, especially against the Th2 response through several cytokines and the differentiation of Tregs in type 1 AIP.

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Title: Interleukin-35 promotes the differentiation of regulatory T cells and suppresses Th2 response in IgG4-related type 1 autoimmune pancreatitis
Authors: Takashi Ito
Toshihiro Tanaka
Koh Nakamaru
Takashi Tomiyama
Takashi Yamaguchi
Yugo Ando
Tsukasa Ikeura
Toshiro Fukui
Kazushige Uchida
Akiyoshi Nishio
Kazuichi Okazaki
Publication date: 01-08-2020
Publisher: Springer Singapore
Keywords: Autoimmune Pancreatitis
Cytokines
Published in: Journal of Gastroenterology / Issue 8/2020
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-020-01689-5

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Interleukin-35 promotes the differentiation of regulatory T cells and suppresses Th2 response in IgG4-related type 1 autoimmune pancreatitis

Abstract

Background

Methods

Results

Conclusions

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Abstract

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