A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 production
Abstract Background A previous study revealed the association between susceptibility to Takayasu arteritis (TAK) and a single nucleotide polymorphism (SNP) rs6871626 located in IL12B, which encodes interleukin (IL)-12p40, a common component of IL-12p70 and IL-23. We investigated the expression of th...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2017-09-01
|
Series: | Arthritis Research & Therapy |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s13075-017-1408-8 |
id |
doaj-8a3f7a3e8f64449bac05aa4aead20c3a |
---|---|
record_format |
Article |
spelling |
doaj-8a3f7a3e8f64449bac05aa4aead20c3a2020-11-24T20:57:12ZengBMCArthritis Research & Therapy1478-63622017-09-011911810.1186/s13075-017-1408-8A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 productionToshiki Nakajima0Hajime Yoshifuji1Masakazu Shimizu2Koji Kitagori3Kosaku Murakami4Ran Nakashima5Yoshitaka Imura6Masao Tanaka7Koichiro Ohmura8Fumihiko Matsuda9Chikashi Terao10Tsuneyo Mimori11Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityCenter for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityDepartment of the Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto UniversityDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityCenter for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityCenter for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityDepartment of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto UniversityAbstract Background A previous study revealed the association between susceptibility to Takayasu arteritis (TAK) and a single nucleotide polymorphism (SNP) rs6871626 located in IL12B, which encodes interleukin (IL)-12p40, a common component of IL-12p70 and IL-23. We investigated the expression of these cytokines in patients with TAK, stratifying them into those with or without the risk allele at the rs6871626 SNP. Methods Plasma levels of IL-12p40, IL-12p70, and IL-23 were quantified in 44 patients with TAK and 19 healthy controls (HCs) by enzyme-linked immunosorbent assays. Monocytes were obtained from 20 patients with TAK and 14 HCs, treated with interferon-γ (IFN-γ) and lipopolysaccharide, and then supernatant cytokines were quantified. In addition, the ratio of IFN-γ+ or IL-17A+ cells to CD4+ T cells was measured by flow cytometric analysis of peripheral blood mononuclear cells. Results The levels of plasma IL-12p40, plasma IL-12p70, and supernatant IL-12p70 were significantly higher in patients with TAK than in HCs, whereas there were no significant differences in the levels of plasma IL-23, supernatant IL-23, or supernatant IL-12p40. The levels of plasma IL-12p70, supernatant IL-12p40, and supernatant IL-12p70 were significantly higher in patients with the risk allele than in those without. The ratio of CD4+IFN-γ+ cells was significantly higher in patients with the risk allele, whereas CD4+IL-17A+ cells showed no differences. Conclusions The rs6871626 SNP in IL12B may influence the increased expression of IL-12p40 and IL-12p70. These enhanced cytokines might play roles in the pathophysiology of TAK.http://link.springer.com/article/10.1186/s13075-017-1408-8Takayasu arteritisVasculitisInterleukin-12Single nucleotide polymorphismMonocytes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Toshiki Nakajima Hajime Yoshifuji Masakazu Shimizu Koji Kitagori Kosaku Murakami Ran Nakashima Yoshitaka Imura Masao Tanaka Koichiro Ohmura Fumihiko Matsuda Chikashi Terao Tsuneyo Mimori |
spellingShingle |
Toshiki Nakajima Hajime Yoshifuji Masakazu Shimizu Koji Kitagori Kosaku Murakami Ran Nakashima Yoshitaka Imura Masao Tanaka Koichiro Ohmura Fumihiko Matsuda Chikashi Terao Tsuneyo Mimori A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 production Arthritis Research & Therapy Takayasu arteritis Vasculitis Interleukin-12 Single nucleotide polymorphism Monocytes |
author_facet |
Toshiki Nakajima Hajime Yoshifuji Masakazu Shimizu Koji Kitagori Kosaku Murakami Ran Nakashima Yoshitaka Imura Masao Tanaka Koichiro Ohmura Fumihiko Matsuda Chikashi Terao Tsuneyo Mimori |
author_sort |
Toshiki Nakajima |
title |
A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 production |
title_short |
A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 production |
title_full |
A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 production |
title_fullStr |
A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 production |
title_full_unstemmed |
A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 production |
title_sort |
novel susceptibility locus in the il12b region is associated with the pathophysiology of takayasu arteritis through il-12p40 and il-12p70 production |
publisher |
BMC |
series |
Arthritis Research & Therapy |
issn |
1478-6362 |
publishDate |
2017-09-01 |
description |
Abstract Background A previous study revealed the association between susceptibility to Takayasu arteritis (TAK) and a single nucleotide polymorphism (SNP) rs6871626 located in IL12B, which encodes interleukin (IL)-12p40, a common component of IL-12p70 and IL-23. We investigated the expression of these cytokines in patients with TAK, stratifying them into those with or without the risk allele at the rs6871626 SNP. Methods Plasma levels of IL-12p40, IL-12p70, and IL-23 were quantified in 44 patients with TAK and 19 healthy controls (HCs) by enzyme-linked immunosorbent assays. Monocytes were obtained from 20 patients with TAK and 14 HCs, treated with interferon-γ (IFN-γ) and lipopolysaccharide, and then supernatant cytokines were quantified. In addition, the ratio of IFN-γ+ or IL-17A+ cells to CD4+ T cells was measured by flow cytometric analysis of peripheral blood mononuclear cells. Results The levels of plasma IL-12p40, plasma IL-12p70, and supernatant IL-12p70 were significantly higher in patients with TAK than in HCs, whereas there were no significant differences in the levels of plasma IL-23, supernatant IL-23, or supernatant IL-12p40. The levels of plasma IL-12p70, supernatant IL-12p40, and supernatant IL-12p70 were significantly higher in patients with the risk allele than in those without. The ratio of CD4+IFN-γ+ cells was significantly higher in patients with the risk allele, whereas CD4+IL-17A+ cells showed no differences. Conclusions The rs6871626 SNP in IL12B may influence the increased expression of IL-12p40 and IL-12p70. These enhanced cytokines might play roles in the pathophysiology of TAK. |
topic |
Takayasu arteritis Vasculitis Interleukin-12 Single nucleotide polymorphism Monocytes |
url |
http://link.springer.com/article/10.1186/s13075-017-1408-8 |
work_keys_str_mv |
AT toshikinakajima anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT hajimeyoshifuji anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT masakazushimizu anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT kojikitagori anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT kosakumurakami anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT rannakashima anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT yoshitakaimura anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT masaotanaka anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT koichiroohmura anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT fumihikomatsuda anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT chikashiterao anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT tsuneyomimori anovelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT toshikinakajima novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT hajimeyoshifuji novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT masakazushimizu novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT kojikitagori novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT kosakumurakami novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT rannakashima novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT yoshitakaimura novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT masaotanaka novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT koichiroohmura novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT fumihikomatsuda novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT chikashiterao novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production AT tsuneyomimori novelsusceptibilitylocusintheil12bregionisassociatedwiththepathophysiologyoftakayasuarteritisthroughil12p40andil12p70production |
_version_ |
1716788494003601408 |