Lesional CD4+ IFN-γ+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis

takashi maehara, Hamid Mattoo, Miho Ohta, Vinay S. Mahajan, Masafumi Moriyama, Masaki Yamauchi, Jefte Drijvers, Seiji Nakamura, John H. Stone, Shiv S. Pillai

研究成果: ジャーナルへの寄稿記事

49 引用 (Scopus)

抄録

Objectives IgG4-related disease (IgG4-RD) is a chronic, systemic, inflammatory condition of unknown aetiology. We have recently described clonally expanded circulating CD4+ cytotoxic T lymphocytes (CTLs) in IgG4-RD that infiltrate affected tissues where they secrete interleukin (IL)-1β and transforming growth factor -β1 (TGF-β1). In this study, we sought to examine the role of CD4+ CTLs in the pathogenesis of IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) and to determine whether these cells secrete interferon-gamma (IFN-γ) at lesional sites. Methods Salivary glands of 25 patients with IgG4-DS, 22 patients with Sjögren's syndrome (SS), 12 patients with chronic sialoadenitis (CS) and 12 healthy controls were analysed in this study. Gene expression analysis was performed on submandibular glands (SMGs) from five patients with IgG4-DS, three with CS and three healthy controls. Infiltrating CD4+ CTLs were examined by quantitative multicolour imaging in tissue samples from 20 patients with IgG4-DS, 22 patients with SS, 9 patients with CS and 9 healthy controls. Results In IgG4-DS tissues, nine genes associated with CD4+ CTLs were overexpressed. The expression of granzyme A (GZMA) mRNA was significantly higher in samples from patients with IgG4-RD compared with corresponding tissues from SS and healthy controls. Quantitative imaging showed that infiltrating CD4+ GZMA+ CTLs were more abundant in patients with IgG4-DS than in the other groups. The ratio of CD4+ GZMA+ CTLs in SMGs from patients with IgG4-DS correlated with serum IgG4 concentrations and the number of affected organs. A large fraction of CD4+ GZMA+ CTLs in SMGs from patients with IgG4-DS secreted IFN-γ. Conclusions The pathogenesis of IgG4-DS is associated with tissue infiltration by CD4+ GZMA+ CTLs that secrete IFN-γ.

元の言語英語
ページ(範囲)377-385
ページ数9
ジャーナルAnnals of the Rheumatic Diseases
76
発行部数2
DOI
出版物ステータス出版済み - 2 1 2017

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Dacryocystitis
Sialadenitis
T-cells
Cytotoxic T-Lymphocytes
Interferon-gamma
Immunoglobulin G
Granzymes
Tissue
Submandibular Gland
Imaging techniques
Transforming Growth Factors
Salivary Glands
Interleukin-1
Infiltration
Gene expression

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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Lesional CD4+ IFN-γ+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis. / maehara, takashi; Mattoo, Hamid; Ohta, Miho; Mahajan, Vinay S.; Moriyama, Masafumi; Yamauchi, Masaki; Drijvers, Jefte; Nakamura, Seiji; Stone, John H.; Pillai, Shiv S.

:: Annals of the Rheumatic Diseases, 巻 76, 番号 2, 01.02.2017, p. 377-385.

研究成果: ジャーナルへの寄稿記事

maehara, takashi ; Mattoo, Hamid ; Ohta, Miho ; Mahajan, Vinay S. ; Moriyama, Masafumi ; Yamauchi, Masaki ; Drijvers, Jefte ; Nakamura, Seiji ; Stone, John H. ; Pillai, Shiv S. / Lesional CD4+ IFN-γ+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis. :: Annals of the Rheumatic Diseases. 2017 ; 巻 76, 番号 2. pp. 377-385.
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title = "Lesional CD4+ IFN-γ+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis",
abstract = "Objectives IgG4-related disease (IgG4-RD) is a chronic, systemic, inflammatory condition of unknown aetiology. We have recently described clonally expanded circulating CD4+ cytotoxic T lymphocytes (CTLs) in IgG4-RD that infiltrate affected tissues where they secrete interleukin (IL)-1β and transforming growth factor -β1 (TGF-β1). In this study, we sought to examine the role of CD4+ CTLs in the pathogenesis of IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) and to determine whether these cells secrete interferon-gamma (IFN-γ) at lesional sites. Methods Salivary glands of 25 patients with IgG4-DS, 22 patients with Sj{\"o}gren's syndrome (SS), 12 patients with chronic sialoadenitis (CS) and 12 healthy controls were analysed in this study. Gene expression analysis was performed on submandibular glands (SMGs) from five patients with IgG4-DS, three with CS and three healthy controls. Infiltrating CD4+ CTLs were examined by quantitative multicolour imaging in tissue samples from 20 patients with IgG4-DS, 22 patients with SS, 9 patients with CS and 9 healthy controls. Results In IgG4-DS tissues, nine genes associated with CD4+ CTLs were overexpressed. The expression of granzyme A (GZMA) mRNA was significantly higher in samples from patients with IgG4-RD compared with corresponding tissues from SS and healthy controls. Quantitative imaging showed that infiltrating CD4+ GZMA+ CTLs were more abundant in patients with IgG4-DS than in the other groups. The ratio of CD4+ GZMA+ CTLs in SMGs from patients with IgG4-DS correlated with serum IgG4 concentrations and the number of affected organs. A large fraction of CD4+ GZMA+ CTLs in SMGs from patients with IgG4-DS secreted IFN-γ. Conclusions The pathogenesis of IgG4-DS is associated with tissue infiltration by CD4+ GZMA+ CTLs that secrete IFN-γ.",
author = "takashi maehara and Hamid Mattoo and Miho Ohta and Mahajan, {Vinay S.} and Masafumi Moriyama and Masaki Yamauchi and Jefte Drijvers and Seiji Nakamura and Stone, {John H.} and Pillai, {Shiv S.}",
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AU - maehara, takashi

AU - Mattoo, Hamid

AU - Ohta, Miho

AU - Mahajan, Vinay S.

AU - Moriyama, Masafumi

AU - Yamauchi, Masaki

AU - Drijvers, Jefte

AU - Nakamura, Seiji

AU - Stone, John H.

AU - Pillai, Shiv S.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Objectives IgG4-related disease (IgG4-RD) is a chronic, systemic, inflammatory condition of unknown aetiology. We have recently described clonally expanded circulating CD4+ cytotoxic T lymphocytes (CTLs) in IgG4-RD that infiltrate affected tissues where they secrete interleukin (IL)-1β and transforming growth factor -β1 (TGF-β1). In this study, we sought to examine the role of CD4+ CTLs in the pathogenesis of IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) and to determine whether these cells secrete interferon-gamma (IFN-γ) at lesional sites. Methods Salivary glands of 25 patients with IgG4-DS, 22 patients with Sjögren's syndrome (SS), 12 patients with chronic sialoadenitis (CS) and 12 healthy controls were analysed in this study. Gene expression analysis was performed on submandibular glands (SMGs) from five patients with IgG4-DS, three with CS and three healthy controls. Infiltrating CD4+ CTLs were examined by quantitative multicolour imaging in tissue samples from 20 patients with IgG4-DS, 22 patients with SS, 9 patients with CS and 9 healthy controls. Results In IgG4-DS tissues, nine genes associated with CD4+ CTLs were overexpressed. The expression of granzyme A (GZMA) mRNA was significantly higher in samples from patients with IgG4-RD compared with corresponding tissues from SS and healthy controls. Quantitative imaging showed that infiltrating CD4+ GZMA+ CTLs were more abundant in patients with IgG4-DS than in the other groups. The ratio of CD4+ GZMA+ CTLs in SMGs from patients with IgG4-DS correlated with serum IgG4 concentrations and the number of affected organs. A large fraction of CD4+ GZMA+ CTLs in SMGs from patients with IgG4-DS secreted IFN-γ. Conclusions The pathogenesis of IgG4-DS is associated with tissue infiltration by CD4+ GZMA+ CTLs that secrete IFN-γ.

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