Natural killer cells control a T-helper 1 response in patients with Behçet's disease

Yukie Yamaguchi, Hayato Takahashi, Takashi Satoh, Yuka Okazaki, Nobuhisa Mizuki, Kazuo Takahashi, Zenro Ikezawa, Masataka Kuwana

Research output: Contribution to journalArticle

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Abstract

Introduction: Behçet's disease (BD) is a multisystem inflammatory disorder, in which a T-helper 1 (Th1)-polarized immune response plays a major role in the pathogenic process. We evaluated the regulatory role of natural killer (NK) cells in Th1-biased immune responses in patients with BD.Methods: We studied 47 patients with BD, including 10 with active disease (aBD) and 37 with inactive disease (iBD), and 29 healthy controls. The activation status and cytotoxic activity of NK cells were examined by flow cytometry. The levels of mRNAs for immune modulatory and cytotoxic molecules in NK cells were determined by quantitative PCR. The IL-12 signal strength in NK cells was determined by assessing the phosphorylation state of its downstream component, signal transducer and activator of transduction 4, by immunoblotting. Finally, NK cells' ability to modulate the Th1 response was evaluated by co-culturing NK cells and T cells without cell contact.Results: CD69+-activated NK cells were significantly increased in aBD compared with iBD or control samples, although their cytotoxic activities were similar. The iBD NK cells showed downregulated IL-12 receptor β2 mRNA levels compared with aBD or control NK cells. The increased IL-13 expression was detected in a subset of BD patients: most of them had iBD. The IL-13 expression level in iBD patients was significantly higher than the level in controls, but was not statistically different compared with the level in aBD patients. The gene expression profile in iBD patients was consistent with the NK type 2 phenotype, and the shift to NK type 2 was associated with disease remission. NK cells from iBD patients showed impaired IL-12-induced signal transducer and activator of transduction 4 phosphorylation. Finally, iBD, but not control, NK cells suppressed IFNγ expression by aBD-derived CD4+ T cells in vitro.Conclusions: NK cells may control disease flare/remission in BD patients via NK type 2-mediated modulation of the Th1 response.

Original languageEnglish
Article numberR80
JournalArthritis Research and Therapy
Volume12
Issue number3
DOIs
Publication statusPublished - 2010 May 11

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Natural Killer Cells
Interleukin-13
Interleukin-12
Transducers
Interleukin-12 Receptors
Phosphorylation
T-Lymphocytes
Messenger RNA
Natural Killer T-Cells
Transcriptome
Immunoblotting
Flow Cytometry
Down-Regulation
Phenotype
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Yamaguchi, Y., Takahashi, H., Satoh, T., Okazaki, Y., Mizuki, N., Takahashi, K., ... Kuwana, M. (2010). Natural killer cells control a T-helper 1 response in patients with Behçet's disease. Arthritis Research and Therapy, 12(3), [R80]. https://doi.org/10.1186/ar3005

Natural killer cells control a T-helper 1 response in patients with Behçet's disease. / Yamaguchi, Yukie; Takahashi, Hayato; Satoh, Takashi; Okazaki, Yuka; Mizuki, Nobuhisa; Takahashi, Kazuo; Ikezawa, Zenro; Kuwana, Masataka.

In: Arthritis Research and Therapy, Vol. 12, No. 3, R80, 11.05.2010.

Research output: Contribution to journalArticle

Yamaguchi, Y, Takahashi, H, Satoh, T, Okazaki, Y, Mizuki, N, Takahashi, K, Ikezawa, Z & Kuwana, M 2010, 'Natural killer cells control a T-helper 1 response in patients with Behçet's disease', Arthritis Research and Therapy, vol. 12, no. 3, R80. https://doi.org/10.1186/ar3005
Yamaguchi, Yukie ; Takahashi, Hayato ; Satoh, Takashi ; Okazaki, Yuka ; Mizuki, Nobuhisa ; Takahashi, Kazuo ; Ikezawa, Zenro ; Kuwana, Masataka. / Natural killer cells control a T-helper 1 response in patients with Behçet's disease. In: Arthritis Research and Therapy. 2010 ; Vol. 12, No. 3.
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abstract = "Introduction: Beh{\cc}et's disease (BD) is a multisystem inflammatory disorder, in which a T-helper 1 (Th1)-polarized immune response plays a major role in the pathogenic process. We evaluated the regulatory role of natural killer (NK) cells in Th1-biased immune responses in patients with BD.Methods: We studied 47 patients with BD, including 10 with active disease (aBD) and 37 with inactive disease (iBD), and 29 healthy controls. The activation status and cytotoxic activity of NK cells were examined by flow cytometry. The levels of mRNAs for immune modulatory and cytotoxic molecules in NK cells were determined by quantitative PCR. The IL-12 signal strength in NK cells was determined by assessing the phosphorylation state of its downstream component, signal transducer and activator of transduction 4, by immunoblotting. Finally, NK cells' ability to modulate the Th1 response was evaluated by co-culturing NK cells and T cells without cell contact.Results: CD69+-activated NK cells were significantly increased in aBD compared with iBD or control samples, although their cytotoxic activities were similar. The iBD NK cells showed downregulated IL-12 receptor β2 mRNA levels compared with aBD or control NK cells. The increased IL-13 expression was detected in a subset of BD patients: most of them had iBD. The IL-13 expression level in iBD patients was significantly higher than the level in controls, but was not statistically different compared with the level in aBD patients. The gene expression profile in iBD patients was consistent with the NK type 2 phenotype, and the shift to NK type 2 was associated with disease remission. NK cells from iBD patients showed impaired IL-12-induced signal transducer and activator of transduction 4 phosphorylation. Finally, iBD, but not control, NK cells suppressed IFNγ expression by aBD-derived CD4+ T cells in vitro.Conclusions: NK cells may control disease flare/remission in BD patients via NK type 2-mediated modulation of the Th1 response.",
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