T helper 2 and regulatory T-cell cytokine production by mast cells

A key factor in the pathogenesis of IgG4-related disease

Mai Takeuchi, Yasuharu Sato, Kyotaro Ohno, Satoshi Tanaka, Katsuyoshi Takata, Yuka Gion, Yorihisa Orita, Toshihiro Ito, Tomoyasu Tachibana, Tadashi Yoshino

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFβ1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease pathogenesis.

Original languageEnglish
Pages (from-to)1126-1136
Number of pages11
JournalModern Pathology
Volume27
Issue number8
DOIs
Publication statusPublished - 2014

Fingerprint

Regulatory T-Lymphocytes
Mast Cells
Immunoglobulin G
Cytokines
Submandibular Gland Diseases
Immunoglobulin E
Salivary Gland Calculi
Mastocytosis
T-Lymphocytes
Submandibular Gland
Helper-Inducer T-Lymphocytes
Interleukin-4
Transforming Growth Factor beta
Interleukin-10
Paraffin
Fluorescent Antibody Technique
Real-Time Polymerase Chain Reaction
Hypersensitivity
Up-Regulation

Keywords

  • cytokine
  • IgE
  • IgG4-related disease
  • mast cells
  • regulatory T cell

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

T helper 2 and regulatory T-cell cytokine production by mast cells : A key factor in the pathogenesis of IgG4-related disease. / Takeuchi, Mai; Sato, Yasuharu; Ohno, Kyotaro; Tanaka, Satoshi; Takata, Katsuyoshi; Gion, Yuka; Orita, Yorihisa; Ito, Toshihiro; Tachibana, Tomoyasu; Yoshino, Tadashi.

In: Modern Pathology, Vol. 27, No. 8, 2014, p. 1126-1136.

Research output: Contribution to journalArticle

Takeuchi, Mai ; Sato, Yasuharu ; Ohno, Kyotaro ; Tanaka, Satoshi ; Takata, Katsuyoshi ; Gion, Yuka ; Orita, Yorihisa ; Ito, Toshihiro ; Tachibana, Tomoyasu ; Yoshino, Tadashi. / T helper 2 and regulatory T-cell cytokine production by mast cells : A key factor in the pathogenesis of IgG4-related disease. In: Modern Pathology. 2014 ; Vol. 27, No. 8. pp. 1126-1136.
@article{d602adc0e8734a4fad6743a00c8b72a4,
title = "T helper 2 and regulatory T-cell cytokine production by mast cells: A key factor in the pathogenesis of IgG4-related disease",
abstract = "IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFβ1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease pathogenesis.",
keywords = "cytokine, IgE, IgG4-related disease, mast cells, regulatory T cell",
author = "Mai Takeuchi and Yasuharu Sato and Kyotaro Ohno and Satoshi Tanaka and Katsuyoshi Takata and Yuka Gion and Yorihisa Orita and Toshihiro Ito and Tomoyasu Tachibana and Tadashi Yoshino",
year = "2014",
doi = "10.1038/modpathol.2013.236",
language = "English",
volume = "27",
pages = "1126--1136",
journal = "Modern Pathology",
issn = "0893-3952",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - T helper 2 and regulatory T-cell cytokine production by mast cells

T2 - A key factor in the pathogenesis of IgG4-related disease

AU - Takeuchi, Mai

AU - Sato, Yasuharu

AU - Ohno, Kyotaro

AU - Tanaka, Satoshi

AU - Takata, Katsuyoshi

AU - Gion, Yuka

AU - Orita, Yorihisa

AU - Ito, Toshihiro

AU - Tachibana, Tomoyasu

AU - Yoshino, Tadashi

PY - 2014

Y1 - 2014

N2 - IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFβ1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease pathogenesis.

AB - IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFβ1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease pathogenesis.

KW - cytokine

KW - IgE

KW - IgG4-related disease

KW - mast cells

KW - regulatory T cell

UR - http://www.scopus.com/inward/record.url?scp=84905441200&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905441200&partnerID=8YFLogxK

U2 - 10.1038/modpathol.2013.236

DO - 10.1038/modpathol.2013.236

M3 - Article

VL - 27

SP - 1126

EP - 1136

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

IS - 8

ER -