TY - JOUR
T1 - Natural killer cells control a T-helper 1 response in patients with Behçet's disease
AU - Yamaguchi, Yukie
AU - Takahashi, Hayato
AU - Satoh, Takashi
AU - Okazaki, Yuka
AU - Mizuki, Nobuhisa
AU - Takahashi, Kazuo
AU - Ikezawa, Zenro
AU - Kuwana, Masataka
N1 - Funding Information:
The authors thank Aya Komori for their excellent technical assistance. The present work was supported by a research grant for intractable diseases from the Japanese Ministry of Health, Labour and Welfare (to MK).
PY - 2010/5/11
Y1 - 2010/5/11
N2 - 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.
AB - 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.
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U2 - 10.1186/ar3005
DO - 10.1186/ar3005
M3 - Article
C2 - 20459787
AN - SCOPUS:77951945881
SN - 1478-6354
VL - 12
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 3
M1 - R80
ER -